Open Access

Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review)

  • Authors:
    • Shengnan Ren
    • Zhanyi Zhang
    • Mengyuan Li
    • Daren Wang
    • Ruijie Guo
    • Xuedong Fang
    • Fangfang Chen
  • View Affiliations

  • Published online on: May 5, 2023
  • Article Number: 71
  • Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Cancer‑testis antigen (CTA) is a well‑accepted optimal target library for cancer diagnosis and treatment. Most CTAs are located on the X chromosome and aggregate into large gene families, such as the melanoma antigen, synovial sarcoma X and G antigen families. Members of the CTA subfamily are usually co‑expressed in tumor tissues and share similar structural characteristics and biological functions. As cancer vaccines are recommended to induce specific antitumor responses, CTAs, particularly CTA subfamilies, are widely used in the design of cancer vaccines. To date, DNA, mRNA and peptide vaccines have been commonly used to generate tumor‑specific CTAs in vivo and induce anticancer effects. Despite promising results in preclinical studies, the antitumor efficacy of CTA‑based vaccines is limited in clinical trials, which may be partially attributed to weak immunogenicity, low efficacy of antigen delivery and presentation processes, as well as a suppressive immune microenvironment. Recently, the development of nanomaterials has enhanced the cancer vaccination cascade, improved the antitumor performance and reduced off‑target effects. The present study provided an in‑depth review of the structural characteristics and biofunctions of the CTA subfamilies, summarised the design and utilisation of CTA‑based vaccine platforms and provided recommendations for developing nanomaterial‑derived CTA‑targeted vaccines.

1. Introduction

The cancer testis antigen (CTA) is a large protein family that is exclusively expressed in the testis, placenta and certain types of malignant tumor, and is involved in the regulation of critical processes during tumorigenesis and development (1). Attributed to the blood-testis barrier, CTAs are categorized as immunogenic tumor-associated antigens and deemed optimal targets for the design of therapeutic cancer vaccines (2). To date, >200 CTAs have been identified and documented in the CT database (, and >100 gene families are highly expressed in malignant tumors. Most genes in the same CTA subfamily are located in adjacent positions on the chromosomes and the encoded proteins generally share similar domains and structural characteristics. In tumor tissues, members of the CTA subfamily are frequently co-expressed and have similar cellular functions. For instance, members of the melanoma antigen family (MAGE) have a highly conserved domain, MAGE homology domain, (MHD), and have essential roles in stress response and cancer progression (3,4). As MAGEs are widely expressed in a wide range of malignancies, vaccines targeting MAGEs have been developed in clinical trials to treat various cancer types, including melanoma and lung cancer (5-7). Therefore, a better understanding of the structural and functional characteristics of the CTA family in malignant tumors is helpful for developing reliable targets for tumor immunotherapy.

Immunotherapeutic strategies targeting CTAs include engineered T-cell receptor T-cell therapy, chimeric antigen receptor T-cell therapy and vaccine-based therapy. Cancer vaccines are and attractive complement or alternative to conventional cancer treatments with great prophylactic and therapeutic potential (8). Cancer vaccines stimulate tumor-specific immune responses through delivering tumor antigens into antigen-presenting cells (APCs) and induce vigorous antitumor immunity to inhibit tumor growth, recurrence and metastasis (9). Compared with other immunotherapeutic strategies, cancer vaccines provide specific, safe and tolerable control of cancer progression. Furthermore, nanomaterials have been utilized to design vaccine platforms, which improved the efficacy during antigen delivery, processing and presentation to T cells (10). A variety of cancer nanomaterial-based vaccines have been designed to deliver peptide/adjuvant or nucleic acid of CTAs. In addition to commonly used inorganic and organic materials (such as polymers and liposomes), dipeptide-based nanotubes, nucleic acid nanostructures, cell membranes and other biomimetic nanomaterials have also proven effective as methods for delivering vaccine compositions to targeted sites (11-14).

So far, cancer vaccines targeting the CTA family exhibited promising efficacy in tumor control at preclinical and clinical stages (15,16). However, the clinical translation of cancer vaccines is hampered by relatively weak immunogenicity and a suppressive tumor microenvironment (TME). Since members of the CTA subfamily usually share homology in structure and expression patterns, attention should be paid to improving the immunogenicity of CTA vaccines. On the other hand, the application of nanomaterials may also serve as an excellent approach to conquering the suppressive TME and generate a profound antitumor response. In fact, delivery of CTA antigens by nanomaterial-derived systems has been demonstrated, with certain results of inhibiting tumor growth and metastasis (13,17). The present review briefly summarized the structural homology and distinct biological functions of the six CTA subfamilies, providing a systematic understanding of CTA antigens and a comprehensive approach for designing cancer vaccines based on CTA (Table I; Fig. 1). The current status and challenges of cancer vaccines targeting CTAs were also summarized, including the results and adverse events of conventional vaccination (DNA vaccines, mRNA vaccines and peptide vaccines). A proposal was made to develop a nanomaterial-derived cancer vaccine, which holds great promise for overcoming the suppressive immune microenvironment and achieving co-delivery of multiple vaccine components.

Table I

Chromosome location and immunogenicity of CTA subfamilies.

Table I

Chromosome location and immunogenicity of CTA subfamilies.

CTALocationTumor typesHumoral responsesCellular responses(Refs.)
MAGEsXq28, Xp21, Xp22, Xq27.2Melanoma, esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma, breast cancer, glioma, NSCLCMelanoma, MM, NSCLCHCC, melanoma, breast cancer(12,24,25, 31-33,37-44)
SSXsXp11.2Seminoma, melanoma, sarcoma, breast cancer, MM, HCC, gynecological cancer, ovarian cancerBreast cancer, MM, gynecological cancer, ovarian cancerHCC, breast cancer, ovarian cancer(41,42,57, 60,61, 65-67,70-73)
GAGEsXp11.23MM, glioblastoma, HCC, ovarian cancer, HNSCC, colorectal cancer, lung cancer, melanomaHCC, melanomaNA(80,84-93)
XAGEsXp11.21-Xp11.3Lung cancer, HCC, prostate cancer, Ewing's sarcoma, melanomaProstate cancer, NSCLC, lung adenocarcinomaLung adenocarcinoma, NSCLC(97-105)
PAGEsXp11.2Prostate cancer, uterus cancer, colorectal cancer, NSCLCNANA(40,107-111)
NY-ESO-1Xq28MLS, SS, osteosarcoma, esophageal cancer, colorectal cancer, breast cancer, thyroid cancer, bladder cancer, lung cancer, adult T cell leukemia, ovarian cancer, HCC, neuroblastomaBreast cancer, ovarian cancer, melanoma, adult T cell leukemia, lung cancer, thyroid cancer, bladder cancer, esophageal cancerBreast cancer, HCC, melanoma, neuroblastoma(38,83,121, 123-138)

[i] CTA, cancer-testis antigen; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; HNSCC, head and neck squamous cell carcinoma; MM, multiple myeloma; MAGE, melanoma antigen; NA, not available; SSX, synovial sarcoma X; GAGE, G antigen.

2. CTA subfamilies

MAGE family

Since first having been identified as a CTA in 1991, the MAGE family is the largest CTA subfamily consisting of >40 members (18,19). Based on expression pattern and chromosomal location, the human MAGE family is generally divided into type I MAGEs and type II MAGEs (20-22). Type I MAGEs, including MAGE-A, -B and -C subfamily members, are considered CTAs due to their restricted expression pattern in adult testicular germ cells and malignancies. Type II MAGEs, including MAGE-D, -E, -F, -G, -H and -L subfamilies and Necdin, are observed in various tissues, such as embryonic and various adult tissues, such as the brain (20,21,23). Given that type I MAGEs are the most studied CTAs in tumorigenesis and anticancer treatments, the structural features and biofunctions of type I MAGEs will be discussed in this subsection.

Biofunction under normal conditions

Type I MAGEs are located on the X chromosome, including MAGE-As (A1-A12) at q28, MAGE-Bs (B1-18) at Xp21 and Xp22 and MAGE-Cs (C1-3) at Xq27.2 (24,25). Most type I MAGEs are broadly expressed in the testis and placenta under normal physiological conditions, indicating their potential roles in germ cell development (26,27). It has been reported that MAGE-As are involved in embryonic and spermatogenesis development, as well as participation in neuron development (26,28,29,30).

Expression specificity and immunogenicity in malignancies

Aberrant activation of MAGEs has been found in various human cancers with different frequencies. It is noteworthy that numerous MAGEs share co-expression patterns in tumors, including MAGE-A1, -A9 and -A11 in laryngeal squamous cell carcinoma with lymph node metastasis (71.0, 64.5 and 77.4%) (31), MAGE-A9 and -A11 in breast cancer (45 and 66.7%) (32) and MAGE-A1, -A3 and -A11 in glioma (64.1, 51.3 and 57.7%) (33). As far as the regulatory mechanism of expression is concerned, most MAGEs are activated by epigenetic reprogramming in malignancies. DNA hypomethylation and histone modification are thought to be responsible for the extensive expression of MAGEs in tumors (3,34). Treatment with the histone deacetylase inhibitor trichostatin A and the DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) synergistically activates the expression of MAGE-A1, -A2, -A3 and -A12 in various cancer cells (35). Furthermore, bioinformatics has confirmed that MAGE-A11 and MAGE-A6 were co-expressed in human prostate cancer and formed a protein complex, which enhanced MAGE-A11 stability by inhibiting the ubiquitination of MAGE-A11 (36).

Owing to the blood-testis barrier, an immune response to MAGEs has been observed in numerous cancer types, which has been summarized in several excellent reviews (12,37,38). Heterogeneous humoral response against MAGE-A4 and -A10 was detected in patients with melanoma, particularly in stage II patients (39). Antibodies against MAGE-A3 were detected in patients with multiple myeloma (MM) and limited levels of autoantibodies against MAGE-B4 and -C2 were detected in patients with non-small cell lung cancer (NSCLC), both at a frequency of 3% (40,41). In patients with hepatocellular carcinoma (HCC), a specific cellular response against MAGE-A1 and -A3 was observed in 23.4% (11/47) and 32.76% (19/58) of patients, respectively (42). More importantly, researchers have demonstrated a significant correlation between MAGE-A3-specific CD8+ T cells and tumor regression in patients with melanoma (43). In breast cancer, MAGE-A10 was considered the most prevalent CTA, which provoked a CD8+ T-cell response (44).

Biofunction in tumorigenesis and progression

In addition to the co-expression pattern in tumors, most MAGEs also share significant homology in structure and are involved in regulating tumorigenesis and cancer development (45-47). The conserved signature domain shared by MAGEs, which is called the MHD, consists of a stretch of 200 amino acids (48). All human MHDs have 46% protein sequence identity and most of them possess a conserved dileucine motif, particularly in MAGE-As with high conservation at 70% (21,49). The major function of MAGEs is interacting with E3 RING ubiquitin ligases to form MAGE-RING ligases (MRLs) and regulate a myriad of processes. Shown by targeted and global proteomics, different MAGEs recognize and bind one specific RING ligase, which impacts ligase activity, specification of novel substrates for ubiquitination and subcellular relocation (22). Specifically, MAGE-A2, -A3, -A6, and -C2 directly bind TRIM28 E3 ubiquitin ligase to reduce p53 and ZNFZ382 protein levels (49,50). In addition to the major role of MRLs, MAGE-As also participate in regulating Cullin-RING ligases (CRLs). MAGE-A11 interacts with S phase kinase-associated protein (Skp2) to modulate substrate specificity of Skp2 and its interaction with cyclin A, regulating cell cycle progression (51). Furthermore, MAGE-B2 serves as a methylation-driven gene facilitating proliferation, migration and invasion of laryngeal cancer cells (52,53).

Furthermore, MAGE-As also impact metabolism via activation of signaling pathways. MAGE-As were proved to sustain cancer cell growth when glycolysis was inhibited (29). Protein kinase AMP activated (AMPK) signaling and autophagy are considered general adaptations of cancer cells in response to metabolic stress during tumor progression and metastasis (54). MAGE-A3/6 was reported to be involved in ubiquitination of AMPK α 1 catalytic subunit through direct interaction, and is also degraded by CRL4-DDB1 and CUL4 associated factor 12 to regulate autophagy and cellular adaptation to nutrition stress (55).

Synovial sarcoma (SS) X (SSX) family

The SSX family consists of nine members (SSX1-9) with high homology (56). According to cytogenetic studies on SS, SSXs were identified as fusion partners of the synaptotagmin (SYT) gene harboring the t(X;18) translocation. SYT-SSX fusion gene expression is observed in nearly all synovial sarcoma tumors and is associated with poor prognosis (57-59).

Biofunction under normal conditions

Mapped at chromosome band Xp11.2, SSX RNAs may be detected in the testis and thyroid at a rather low level, but the proteins are observed only in the testis, particularly in early spermatogenic cells (57,60,61). SSX proteins are distributed in the nucleus and the homology between SSX and Kruppel-associated box (KRAB) domain indicates their role as transcriptional repressors (59,62,63). In addition, SSX proteins are expressed in undifferentiated mesenchymal stem cells but are downregulated after the differentiation of osteocytes and adipocytes, suggesting their involvement in stem cell differentiation (64).

Expression specificity and immunogenicity in malignancies

Members of the SSX family are widely co-expressed in various tumors, including seminomas (SSX1/2/4, 58%) (65), melanoma (SSX2/3/4, 40%) (66) and sarcomas (11.8-94.1%) (67). It was revealed that SSX proteins are normally expressed in spermatogonia cells, mainly due to genome-wide demethylation (68). Of note, similar demethylation patterns were observed in tumor cell lines and tumor tissues (69).

Immune responses against SSXs have been widely reported in several types of cancer. Recently, T-cell responses to SSX2 were reported in 10.64% of patients with early- or advanced-stage HCC (42). Antibodies against SSX2 have been detected in patients with breast cancer (2%) and MM who have received allogeneic stem cell transplantation (41,70). Furthermore, the peptide epitope of SSX2 was identified to have the potential to react with anti-SSX2 antibodies in the serum of patients with breast cancer and to induce a specific T-cell response in vitro (71). In addition to SSX2, immune response against SSX4 is present in gynecological cancer (72). In epithelial ovarian cancer, antibodies against SSX2 and SSX4 have been detected in 2 out 120 patients and specific T-cell response to SSX4 was also identified with SSX4-derived epitopes. These early findings demonstrated the immunogenicity of SSXs and provide SSXs as the primary CTAs used to design cancer vaccines (73).

Biofunction in tumorigenesis and development

Similar to MAGEs, high homology is also observed between SSXs. Two main domains are characterized in SSXs: The N-terminal portion with high homology to KRAB consisting of 75 highly charged amino acids (66) and the SSX repressive domain (SSXRD) formed by 33 amino acids at the C-terminus (62).

Functionally, SSXs have a significant oncogenic role in various tumor types through their KRAB and SSXRD domains. Translocation of the SSXRD domain to the C-terminal end of SYT occurs in SS to form the SYT-SSX fusion oncogene, and the chimeric products of SYT-SSXs exhibit aberrant activity to promote cellular transformation during SS development (74,75). Transactivation of SYT-SSX1/SSX2 proteins leads to transcriptional activation in tumors, whereas unrearranged SSX1/SSX2 proteins have an inhibitory effect due to the repressive KRAB domain at the N-terminus (62). PcG proteins are observed in various types of cancer and associated with pericentromeric heterochromatin region and tumor development (76). Through interaction with various PcG factors via KRAB and SSXRD domains, SS18-SSX and SSX negatively regulate genes involved in multicellular differentiation, stem cell renewal, embryonic development in drosophila and vertebrates, and tumor progression (66,77,78). Researchers have found that SSX genes are co-localized with B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1), which is a core factor of polycomb repressive complex 1 (PRC1). In addition, there is an intrinsic nucleolar localization signal induced by cellular stress, which consequently leads to dissociation of SSX from Bmi1, resulting in downregulation of SSX protein activity (79).

G family (GAGE)

GAGE antigens are typical CTAs frequently expressed in various types of cancer, as well as germ cells in the testis and ovary. The GAGE family comprises at least 16 highly conserved genes.

Biofunction under normal conditions

GAGEs are mapped to chromosome X p11.23 and each of them is located in one of an identical number of highly conserved tandem repeats (80). GAGE proteins are distributed in nuclei and cytoplasm of spermatogonia and primary spermatocytes (81). Beyond the testis, GAGEs expression was also found in primordial germ cells of the gonad primordium, which is maintained until adulthood (82). GAGE proteins were indicated to be expressed in human ectodermal and mesodermal derivatives, implying that they are related to maintaining ground-state pluripotency (83).

Expression specificity and immunogenicity in malignancies

GAGEs are aberrantly activated in 76% glioblastoma and negatively associated with the 2-year overall survival (OS) rate (84). GAGE genes are also highly expressed in head and neck squamous cell carcinoma (81.5%, 22/27) (85). Furthermore, GAGE-1 expression is upregulated in 43.3% of hepatocellular carcinoma tissue (26/60) and GAGE-1/-2 are co-expressed in 26.8% of ovarian cancer tissues (11/41) (86,87). Activation of GAGEs was observed in MM, colorectal cancer, lung cancer and papillary and follicular thyroid cancer (88-91). Like that of most CTAs, GAGE expression is regulated by epigenetics. In breast cancer, for instance, high levels of promoter methylation of GAGE were detected by methylation-specific PCR analysis and enrichment of H3K4me3 was observed to be correlated with different expression levels of GAGEs (92).

Owing to its restricted expression in testis and ovary, antibody against GAGE-1 was reported in patients with HCC (23.33%), liver cirrhosis (13.1%) and hepatitis B (3.3%), as well as normal human individuals (3.4%) (86). Taking serum from patients with melanoma as the specific primary antibody, autoantibodies against GAGE were detected in the serum of 4/72 patients, whereas none were observed in 72 healthy controls (93).

Biofunction in tumorigenesis and development

Unlike MAGEs and SSXs, which have highly conserved protein domains, GAGEs have no distinct secondary or tertiary structure (94), indicating that they are intrinsically disordered proteins despite the homology in their amino acid sequences.

GAGE protein expression was identified in multiple tumors, including neuroblastoma, esophageal carcinoma and stomach cancer (80). Levels of GAGE protein were associated with a poor differentiation level of malignant thyroid diseases, indicating a role in tumorigenesis (91). Cellular levels of the apoptotic regulators interferon regulatory factor 1 and nucleophosmin were regulated by GAGE expression, which contribute to resistance to cytotoxic agents (95). Furthermore, GAGEs are also involved in the development of radiation resistance through the regulation of chromatin accessibility and DNA repair efficiency (96).

X antigen family (XAGE)

The XAGE family, consisting of at least 3 homologous clusters (XAGE-1, -2 and -3), was identified after screening the expressed sequence tag database ( for PAGE family member 4 (PAGE-4) homologous genes. Members of the XAGE family are clustered on chromosome X (Xp11.21-Xp11.3), where SSXs, GAGEs and MAGE-D, -H, -I and -J were also mapped (97). XAGEs are mainly expressed in placenta, testis and sarcoma tissues, except XAGE-3, which is expressed only in placenta but not the testis or any tumor lesions (97).

Expression specificity and immunogenicity in malignancies

A total of four transcript variants, XAGE-1a, -1b, -1c, -1d, have been identified in various types of tumor (98), including lung cancer (XAGE-1b and XAGE-1d, 30.6%) (99), hepatocellular carcinoma (XAGE-1b, 64.4%; XAGE-1c, 15.6%; XAGE-1d, 26.0%) (100,101), prostate cancer (XAGE-1, 35,2%) (102) and Ewing's sarcoma (XAGE-1, 33.3%) (97). Of note, XAGE-1b is expressed in almost all melanomas (103).

ELISA of 278 patients with prostate cancer revealed that antibodies against XAGE-1 were detectable in two stage-D2 patients, but not in healthy controls (102). Humoral response to XAGE-1b was also confirmed in patients with NSCLC (104). T-cell response against XAGE-1b was reported in lung adenocarcinoma tissues and T-cell and B-cell epitopes of XAGE-1b protein were identified by Yazdi et al (105).

Biofunction in tumorigenesis and development

All XAGE transcripts contain a relatively large secondary open reading frame, which encodes putative proteins in homology with XAGE-1 primary protein (97). Considering strong homology between XAGEs, tumor vaccines targeting multiple XAGEs may become a novel therapeutic strategy for generating efficient antitumor effects.

The association between high levels of XAGE expression and poor outcomes in patients with cancer implies that XAGEs may have an important role in tumorigenesis and cancer progression. Patients with HCC with positive XAGE-1 mRNA expression had a relatively lower 2-year survival rate (101). In particular, XAGE-1b promoted adenoid cystic carcinoma progression by regulating the cell cycle (shortening the G0/G1 and prolonging the G2/M phase) and enhanced resistance to apoptotic effects induced by tumor necrosis factor-α (106).

PAGE family

The PAGE family is a GAGE-like gene family that was identified by a combination of experimental expression analyses and computerized database mining (107). The PAGE family consists of five members, namely PAGE1-5, which share a significant homology in amino acid sequence (108). Different from the other four members, PAGE-4 is the most well-studied, with significant expression in prostate cancer and therapeutic potential.

Expression specificity and immunogenicity in malignancies

By Northern blot, PAGE-1 RNA expression was revealed in prostate cancer and uterine cancer tissues. Expression of PAGE-2 was detected in the colorectal cancer cell line Caco-2 and PAGE-4 is highly expressed in prostate cancer (109,110). The expression pattern of PAGEs is not as restricted in neoplasms, such as prostate cancer and colorectal cancer, as other CTA families mentioned above (107,111). PAGE-1 mRNA may also be found in certain normal tissues, including testis, prostate, uterus and placenta, which signifies that more attention should be paid to develop PAGE-targeted immunotherapy, avoiding severe side effects (117).

The expression of PAGEs is associated with the demethylation status of CpG residues within regions proximal to the transcription start sites. PAGE-2 expression may also be activated by 5-aza-CdR treatment in colorectal cancer cell lines (111). As to immunogenicity, humoral response against PAGE-3 was reported in 3.8 and 2.9% of patients with NSCLC from two cohorts, but not in patients with benign lung disease (40).

Biofunction in tumorigenesis and development

PAGEs are small proteins containing 102-146 amino acids with high abundance of hydrophilic/charged residues and certain hydrophobic residues, indicating that they are intrinsically disordered proteins (112). As an ensemble of interconverting conformations without rigid 3D structure, these proteins are compared to 'dancing protein cloud' and are inclined to partially form instantaneous secondary structures, which function as potential ligand binding sites in succession (112-115).

PAGEs have important biological roles as cellular transformation promoters and metastasis suppressors in cancer. PAGE-4 is also highly expressed in high-grade prostatic intraepithelial neoplasia and was considered a tumorigenic precursor (116). Consistent with that, upregulated PAGE-4 expression protects cancer cells from oxidative stress through modulating the MAPK signaling pathway (117). PAGE-4 interacts with and potentiates proto-oncogene c-Jun transactivation through conformational changes, indicating a new vulnerability of prostate cancer (118).

New York esophageal squamous cell carcinoma 1 (NY-ESO-1)

NY-ESO-1 was cloned from a cDNA library of esophageal cancer using recombinant cDNA library serological analysis technology in 1997 (119). Structurally, it is a 180 amino acid-long protein, containing epitopes of both cellular and humoral responses in the glycine-rich N-terminal and hydrophobic C-terminal regions (120).

Biofunction under normal conditions

According to information from the CTDatabase (, the NY-ESO-1 family, containing cancer/testis antigen 2 (CTAG2) and cancer/testis antigen 1B (CTAG1B, official name of NY-ESO-1), maps to the Xq28 region of the X chromosome (121). Under normal conditions, the expression of NY-ESO-1 antigen has been documented in human testis, and in germ cells of fetus testis and ovaries at 13-18 weeks; it plateaus at 22-24 weeks, and subsequently, it decreases rapidly (121). NY-ESO-1 was also observed to be upregulated during the differentiation process within developing spermatogonia (122).

Expression specificity and immunogenicity in malignancies

As a well-studied CTA, NY-ESO-1 protein expression has been identified in a variety of cancers, but not in normal adult tissues except immune-privileged organs, such as the testis and placenta (123). NY-ESO-1 has been detected in myxoid liposarcoma (45/64, 70.3%) (124), SS (20/25, 80.0%) (123), osteosarcoma (3/9, 33.3%) (125), esophageal cancer (83/227, 36.6%) (126), colorectal cancer (13/60, 21.7%) and breast cancer (37/97, 38.1%) (127), In addition, upregulated NY-ESO-1 was found in metastatic tumor sites and to be associated with high risk of recurrence and a poor survival rate (128-131). So far, the expression pattern of NY-ESO-1 has been fully illustrated by several excellent reviews (121,132-134). Owing to the specific expression pattern, therapeutic strategies targeting NY-ESO-1 have achieved certain effects with limited off-target events (133), which will be discussed in the next section. Like most CTAs, regulation of NY-ESO-1 expression in tumors is also mediated by several epigenetic events, involving tightly controlled sequential interaction of histone deacetylases, histone methyltransferase, DNA methyltransferases and transcription factors (121). There is a clear correlation between high NY-ESO-1 antigen expression and the hypomethylation status of promoters in various tumor cell types (83).

NY-ESO-1 is one of the most immunogenic CTAs in various cancer types. Humoral response to NY-ESO-1 was reported in several cancers, including breast cancer (73%), ovarian cancer (30%), melanoma (9.4%), adult T-cell leukemia (11.6%), lung cancer (4-12.5%), thyroid cancer (36%), bladder cancer (12.5%) and esophageal cancer (13%) (38,135). In terms of cellular response, NY-ESO-1-specific T-cell response was detected in 10.64% of patients with HCC (42). Patients with melanoma who had NY-ESO-1 antibodies exhibited CD8+ T-cell responses, and NY-ESO-1-specific T cells in patients with neuroblastoma were reported to produce interferon-γ (136-138).

Biofunction in tumorigenesis and development

NY-ESO-1 expression in cancer tissues was indicated to be associated with lymph node metastasis, higher differentiation grade and advanced clinical stage, indicating an important role in regulating tumor development and progression (121,134). In MM, NY-ESO-1 knockdown caused impaired growth of MM cell lines and reduced osteolytic lesions, and it upregulated the expression of E-cadherin, p21 and p53 in vivo (139). Furthermore, NY-ESO-1 expression in mesenchymal stem cells was downregulated after differentiation, suggesting a role in cell differentiation (38). Furthermore, a positive correlation between NY-ESO-1 and forkhead box P3 levels was reported in the TME of NSCLC (140).

3. Design and application of CTA-based tumor vaccines

Due to their restricted expression pattern in tumors, CTAs are promising targets for therapeutic vaccines. Certain CTA subfamilies, such as MAGEs, are more attractive candidates for the development of cancer vaccines. Thus far, numerous CTA-based tumor vaccines have been developed and are able to induce antitumor response through direct administration as a DNA vaccine, RNA vaccine or protein vaccine (Table I). In addition, nanomaterial-derived delivery systems have caught the attention of researchers, with higher delivery efficiency and induced robust immune response. These vaccine platforms are presented in the following sections (Fig. 2).

Design of CTA-based cancer vaccines
Targeted antigens of cancer vaccines

As mentioned previously, numerous CTAs are expressed in various tumor tissues at different frequencies. However, not all of them have been used to construct cancer vaccines due to the irregular expression frequencies and relatively low immunogenicity (141). MAGE, NY-ESO-1, SSX, cancer-testis SP-1 (CTSP-1), TTK protein kinase (TTK1), insulin-like growth factor II mRNA-binding protein 3 (IMP-3), sperm lysozyme-like protein 1 (SLLP1), placenta enriched 1 (PLAC1), lactate dehydrogenase C, sperm autoantigenic protein 17 (sp17) and PRAME nuclear receptor transcriptional regulator (PRAME) are the most widely-used CTAs in tumor vaccines at present, which have demonstrated promising results in preclinical research (15,142-146). However, vaccines targeting SSX, CTSP-1, SLLP1 and PLAC1 are barely used in clinical trials due to limitations regarding safety, stability and effectiveness (147). According to data from, NY-ESO-1 and MAGEs are the most widely-used CTAs to treat malignancies with high immunogenicity (accounting for 37 and 36% of all clinical trials, respectively). They may stimulate both cellular and humoral immune responses with considerable safety and antigenicity (148). Vaccines targeting LY6K (also known as URLC10), TTK1, IMP-3, PRAME and sp17 are also used in several clinical trials to control tumor progression (

Melanoma, lung cancer and ovarian cancer have been categorized as CTA-high-expressing malignancies, breast cancer and prostate cancer as CTA-moderately-expressing malignancies, and colorectal cancer, kidney cancer and pancreatic cancer as CTA-low-expressing malignancies (83). Consistently, most CTA-based vaccine trials were performed in patients with melanoma (72.36%), particularly those targeting MAGEs and NY-ESO-1. According to data from clinical trials, lung cancer is the second-most common malignancy treated with CTA vaccines and therapeutic targets are LY6K, TTK and IMP-3 (149). There have been fewer clinical trials on the use of CTA vaccines for the treatment of ovarian cancer than lung cancer and the commonly used target is NY-ESO-1, similarly to the role of NY-ESO-1 in melanoma (Fig. 3).

DNA vaccines

In addition to gene targets, the form of antigen delivery also has an important impact on vaccination efficacy, which includes DNA vaccines, RNA vaccines and peptide vaccines. Among them, DNA vaccine is a well-studied type of vaccination with the longest history. DNA vaccines may induce both cellular and humoral responses and have several advantages, such as low incidence of side effects, high stability, simplicity and repeated administration (150). Innate immune response may also be stimulated by DNA vaccine due to the presence of CpG motifs and the double strand nucleotide (151). Taking melanoma as an example, studies using multiple melanoma-associated antigens are ongoing, combining them with molecular adjuvants to enhance the antitumor effect (152).

RNA vaccines

mRNA vaccine represents a promising immunotherapy approach with rapid development, safe administration and relatively low-cost manufacture (153). Compared to DNA vaccine, advantages of mRNA vaccine are as follows: i) Protein expression rate and magnitude of mRNA are higher than for DNA vaccines; ii) unlike DNA vaccines, there is no insertional mutagenesis for mRNA vaccines, which do not integrate into the genome (8); and iii) production of mRNA vaccines is less time-consuming and they are less comprehensive to manufacture than plasmid DNA (154,155). In general, mRNA vaccine has attracted widespread interest for the treatment of both infectious disease and malignancies (156).

Peptide vaccines

Peptide vaccines are characterized by better safety and tolerance without any serious adverse events in comparison to traditional anti-tumor therapies and are considered a promising vaccination approach, which directly delivers synthetic or natural tumor-specific, -associated peptide to induce antitumor effects (157,158). There are several advantages of peptide-based therapeutic cancer vaccines, including convenient production, low carcinogenic potential, cost-effective manufacture, high chemical stability and insusceptibility to pathogen contamination (156). Peptide-based vaccine has become a major focus of cancer vaccine study with promising clinical possibilities. Peptides used for cancer vaccines usually consist of small peptides (generally 7-14 amino acids) with immunogenicity expressed on target cells. Peptide vaccines have been tested in clinical trials for multiple cancers, including esophageal cancer (159,160), melanoma (161), lung cancer (162,163), head and neck squamous cell carcinoma (164) and pancreatic cancer (165). Application and challenges of CTA-based cancer vaccines

DNA vaccines

SSXs and MAGE-As are commonly used targets of DNA vaccines to generate antigen-specific CD4+ and CD8+ T-cell responses (166,167). Taking advantage of the homology between MAGE-As, researchers designed and optimized a consensus MAGE-A DNA vaccine to treat melanoma, which was able to cross-react with numerous MAGE-A isoforms. Immunization with the MAGE-A vaccine in mice induced robust CD8+ T-cell responses against multiple isoforms (14/15), exhibited cytotoxic effects to significantly inhibit tumor growth and prolonged mouse survival to a median of 50 days, which was 2-fold of that of the control group (168). SSXs are also widely used in cancer vaccines to induce humoral and cellular responses (15,176,169,170). In a previous report, DNA vaccine encoding SSX2 was reported to induce enhanced peptide-specific immune responses and cytotoxic T cells were detectable in mice immunized with modified SSX2 plasmid DNA vaccine (176). In addition to single-gene DNA vaccines, fusion-gene DNA vaccines are being studied and have demonstrated higher immunogenicity. In preclinical research, both SSX2-MAGEA3 and MAGEA3-SSX2 DNA vaccines achieved improved antitumor effects in the treatment of esophageal cancer compared to either MAGEA3 or SSX2 DNA vaccine (15).

Safety concerns regarding DNA vaccines are usually hypersensitivity reaction and mutation risk. In a phase I/II clinical trial for prostate cancer, 50% (13/26) of patients exhibited a delayed-type hypersensitivity reaction after treatment with naked DNA of proteasome 20S subunit alpha and CD86 (171). In another phase I trial of erb-b2 receptor tyrosine kinase 2-postive breast cancer, mild to moderate complications were reported in 82% of patients with injection site reactions, 36% with fatigue and 33% with flu-like syndrome (172). Furthermore, DNA vaccines may integrate into the host genome and increase the risk of genomic alteration; the production of anti-DNA autoantibodies may also limit their application (173).

Despite the efficacy and safety demonstrated in clinical trials, clinical translation of DNA vaccines targeting CTAs remains limited, mainly by two factors: Immunosuppressive TME and low immunogenicity profiles in human studies. According to a previous report, optimized SSX2 DNA vaccination led to increased expression of programmed cell death 1 (PD-1) and PD-1 ligand 1 on CD8+ T cells and tumor cells, respectively, signifying the importance of combined treatment with chemotherapy, radiation therapy and immune checkpoint blockade (2,150,174). Conversely, strategies to improve immunogenicity have been categorized into several aspects, including antigen selection, vaccine construct optimization and delivery method diversity (167). For antigen selection, homology between CTA subfamily members should be considered to avoid safety events and personalized antigens are universally recommended. Vaccine construct design is also responsible for DNA vaccine efficacy. Future design should pay more attention to codon optimization, promoter selection and plasmid vector backbone, as well as adjuvant selection (167).

Effective delivery methods have an important role in DNA vaccination. In general, it is more complex to deliver DNA vaccine than RNA vaccine due to its larger dimension and the necessity for nuclear localization. Plasmids containing target sequences are usually administered directly into the tumor site to produce specific antigens, as well as by mucosal delivery and intramuscular injection (171). Electroporation and intradermal needle-free delivery system were recently developed to enhance vaccination efficacy (175). Furthermore, rapid advancements in biomaterials have facilitated improvements in the efficacy of DNA vaccines (176). Nanoparticles (liposomes or polymeric particles) are recommended to deliver DNA vaccines to target cells, which significantly enhanced encapsulation efficiency and stability, improved cellular uptake and avoided toxicity (176,177). However, the hallmarks of DNA vaccines are their ability to present native conformational immunogens and prime both humoral and cellular immune responses (167). DNA vaccines remain a well-accepted strategy with their stability, scalability and low cost for manufacture, and it is worthwhile to make efforts to develop and investigate methods with improved delivery efficacy (176).

mRNA vaccines

A phase I/IIa clinical trial applied RNA vaccine encoding five tumor-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin and a trophoblast glycoprotein named CV9201) to treat 46 patients with NSCLC. Administrated intradermally, CV9201 generated antigen-specific immune responses in 63% of patients, and the median progression-free survival (PFS) and OS were prolonged to 5.0 [95% confidence interval (CI), 1.8-6.3] months and 10.8 (95% CI, 8.1-16.7) months, respectively. The two- and three-year survival rates were 26.7 and 20.7%, respectively. Furthermore, only mild to moderate adverse events were observed in most patients (16). Similar to DNA vaccines, a combined treatment strategy was recommended to conquer the immunosuppressive TME and to improve outcomes. mRNA-based vaccine encoding six NSCLC antigens (NY-ESO-1, MAGE-C1, MAGE-C2, 5T4, survivin and MUC-1) was utilized in a phase Ib clinical trial in combination with local radiation. Monitoring data revealed increased antigen-specific humoral immunity and cellular immunity in 80 and 40% of patients, respectively. This vaccination has achieved significantly prolonged PFS and OS at 2.87 (95% CI 1.43-4.27) months and 13.95 (95% CI 8.93-20.87) months, respectively (178). Furthermore, researchers recently reported an intravenous-administrated liposomal RNA vaccine (RNA-LPX), which encoded four non-mutated, tumor-associated antigens, including NY-ESO-1, MAGE-A3, tyrosinase and transmembrane phosphatase with tensin homology. For 89 patients with melanoma with treatment-refractory tumors (previous checkpoint inhibitor treatment), vaccination induced a durable antigen-specific cytotoxic T-cell response and a higher tumor regression rate was achieved at 35% after combined treatment with anti-PD-1 (179).

In general, adverse events of mRNA vaccination are mild to moderate, such as flu-like syndrome and injection site reaction. Recently, safety concerns about mRNA vaccines were raised, as a higher occurrence of adverse effects was observed, particularly grade 3 adverse reactions, including anaphylactic shock, myocarditis and pericarditis, cytokine release syndrome and cerebral venous thrombosis (180,181). Furthermore, modified mRNA may combine with serum proteins and form a vascular occlusion, which has potential toxicity (182). In a phase I/II clinical study (NCT03639714), patients with advanced metastatic cancers were treated with mRNA vaccine encoding neoantigen. Most of them were well-tolerated but one patient experienced pyrexia, duodenitis and increased transaminases and hyperthyroidism (183). mRNA vaccine may be administered by various methods, such as intradermal, intranasal, subcutaneous, intranodal, intratumoral, intramuscular and intravenous injection (184). Thereafter, delivery to target cells is achieved usually by lipid-based nanoparticles to protect mRNA from degradation and may significantly improve the delivery efficiency of mRNA vaccines (180). Viruses may also be designed to deliver mRNA encoding peptides that are later displayed by tumor cells and/or other cells (185). Furthermore, peptide vectors and polymer vectors may also facilitate the delivery of mRNA vaccines (186).

However, there are still several points to be fully elucidated concerning the specific mechanism of mRNA vaccine delivered to the immune system, and strategies to overcome the instability of mRNA, as well as to improve the effectiveness of most vaccines, require to be developed (148). Furthermore, the immunosuppressive TME remains the most significant hurdle for mRNA vaccines to induce a robust antitumor effect (8). Future investigations should pay more attention to improving antigen expression efficacy and duration, as well as to promoting antigen presentation efficiency.

Peptide vaccines

Similar to DNA vaccines, MAGEs and NY-ESO-1 are also the most common targets of peptide anticancer vaccines. A previous clinical trial reported significant tumor regression observed in 28% of patients with melanoma (7/25) who received peptide vaccine treatment targeting MAGE-3.A1, but no cytotoxic T-lymphocyte (CTL) responses were detected. In particular, complete tumor regression was observed in two patients who survived >2 years after the treatment (5). Vaccination with human leukocyte antigen (HLA)-A2-binding NY-ESO-1 peptides generated detectable specific antibody in 41.7% (5/12) of patients with metastatic tumors expressing NY-ESO-1, and peptide-specific CD8+ T-cell reactions were detected in 4 of 7 NY-ESO-1 antibody-negative patients (136). In a phase II clinical trial using peptide vaccine targeting three CTAs (TTK, LY6K, IMP-3), LY6K-, IMP3- and TTK-specific CD8+ T-cell responses were observed in 63, 60 and 45% of patients with esophageal cancer, respectively. Of note, the median survival time of HLA-A*2402-positive groups were improved to 4.6 and 2.6 months, respectively (160). On the other hand, adjuvants are usually applied to induce more efficient T-cell responses in combination with CTA peptides. For instance, the immunostimulant AS15 was administered with recombinant MAGE-A3 protein to enhance the antitumor effect in 25 patients with resected stage IIB-IV melanoma (NCT01425749), and durable antibody responses were observed in all patients, as well as T-cell response in sentinel immunized nodes. Either injected intramuscularly (Group A, n=13) or intradermally/subcutaneously (Group B, n=12), MAGE-A3/AS15 vaccination achieved multifunctional CD4+ T-cell responses to MAGE-A3 in 64% of patients (16/24) and prolonged OS to two years in 90% of patients (187).

In terms of adverse events of peptide vaccines, erythema is the most frequently encountered, while rare events include nausea, increased aspartate aminotransaminase, diarrhoea, myalgia and fatigue. Peptides given alone do not elicit strong immune responses in vivo due to quick degradation, absence of danger signals required for APC activation and a lack of costimulatory ability (188). These limitations may be overcome by appropriate formulations. Antigen peptides, adjuvants, as well as targeting sequences, may be encapsulated into a single package that generates a strong T cell-mediated response (188). Poly (lactic-co-glycolic acid) (PLGA) and liposomes are the most widely used drug delivery applications and have been studied for numerous years with great biosafety and biodegradability (189). In a recent preclinical study, PLGA nanoparticles were designed to deliver an immunogenic peptide to enhance antigen delivery and presentation, and generated a robust CD8+ CTL response against multiple myeloma in comparison with free peptide (189).

Peptide vaccines are promising therapeutic approaches with safety, good tolerance and effective immunization (157). A general concern of peptide-based vaccines is the relatively low frequency of CD8+ T and CD4+ T-cell responses (190,191). Thus, challenges are still to be overcome to develop peptide vaccines in the future, which include identification of immunogenetic and neoepitopes, and stimulation of more effective T-cell responses (158).

Nanomaterial-derived vaccine

In spite of the frustrating results of tumor vaccines in clinical trials, attempts never ceased to improve the efficacy of vaccination cascades, including antigen identification, antigen encapsulation, antigen delivery, antigen release and antigen presentation (10). Nanomaterials have attracted increasing attention due to their potential to enhance the cancer vaccination cascade and facilitate antitumor effect with less off-target events. Widely used nanomaterials for developing tumor vaccines include polymeric nanomaterials, endogenous nanocarriers, lipid-based nanoparticles and biomimetic cell membrane-derived nanosystems (10,192). In general, nano vaccines are produced via electrostatic interaction, covalent linking and hydrophobic interaction to ensure efficient co-encapsulation of antigens as well as adjuvants (193). The antigens and adjuvants released from nano vaccine systems may effectively stimulate the maturation of dendritic cells, which in turn induce the effector T-cell response via cross-presentation and cytokine secretion. Furthermore, cross-presentation, mediated by antibody-antigen immune complex uptake via Fcγ receptors on APCs, also holds significant potential to stimulate long-term antitumor cellular immunity (194). Compared with conventional vaccines, nanovaccines share advantages of increased immunogenicity and co-delivery of multiple antigens, prolonged biological activity, enhanced bioavailability, controlled antigen release and protection of antigens from degradation (195,196).

Due to improved delivery efficiency, nanovaccines have markedly expanded targeted antigens and facilitated the development of individualized vaccines. However, CTA-targeted nanovaccines are still to be fully investigated despite these advantages mentioned above. In a preclinical trial, nanovaccines loaded with MAGE-3 peptides have demonstrated great anti-tumor activity in mice with transplanted gastric cancer and the tumor inhibition rate was as high as 37.81% after treatment (197). In this research, peptide/chitosan was conjugated with deoxycholic acid nanoparticles to encapsulate MAGE-3 peptide, and vaccination resulted in the generation of MAGE-3-specific CTLs and achieved significant tumor regression. Nanoparticle assembled from pyruvate dehydrogenase E2 subunit effectively delivered NY-ESO-1 and MAGE-A3 and achieved an additive effect to induce a specific cell-mediated response resulting in 15-fold and 9-fold increases in cytotoxicity targeting cancer cells, respectively (17). Recently, Verma et al (13) designed a self-assembled peptide-based nanotube entrapping a MAGE-3-derived peptide (F-ΔF-M3) to increase the stability and cellular uptake of M3. After immunization, CTL responses were provoked in mice and led to a remarkable inhibition ratio of tumor growth at 41% (13). In another recently published phase I clinical trial, NY-ESO-1 expression in dendritic cells was induced after delivery via a modified lentivirus-based vector LV305 to treat 39 patients with sarcoma and other types of solid tumor (melanoma, non-small cell lung cancer, ovarian cancer and breast cancer). After intradermal injection, disease control was achieved in 56.4% of all patients, and of note, in 62.5% of patients with sarcoma. NY-ESO-1-specific CD4+ and/or CD8+ T cells were generated in 52% of all patients (57% of sarcoma patients), and median PFS reached both 4.6 months for all patients (95% CI, 2.7-11.7 months) and patients with sarcoma (95% CI, 2.5-8.6 months) (198).

Due to repeat administration of cancer vaccines and slow degradability of delivery materials, they may accumulate and cause toxicity in the liver (199). While membrane vesicles are usually considered ideal vectors to cargo vaccine components, the complex contents in those vesicles may cause impaired glucose tolerance and fasting hyperglycemia, and prolong in vivo residence due to difficult metabolism (200). Genetically modified membrane vesicles may also cause symptoms such as fatigue and fever, or even continuous tumor development, which probably resulted from cargo in membrane nanovesicles (201,202). Mesoporous silica nanoparticles have been considered a classic delivery platform for cancer vaccines with multiple advantages, but the inert Si-O-Si framework may prevent degradation and lead to long-term biosafety issues (203). Furthermore, the multicomponent hybrid nanomaterials may cause complex biodegradation and excretion problems, and potential toxicity is another concern of metal ions and organic nanomaterials (204).

It has been well accepted that nanovaccines represent a novel anticancer strategy. Given the broad activation of CTAs in various cancer types and homology among subfamilies, nanovaccine targeting one or more CTAs is expected to facilitate antitumoral effects. However, nanovaccines have several drawbacks, including fast clearance, and the mechanisms by which nanoparticles are excreted from organisms after cellular uptake/targeting remain largely elusive (179). In addition, the effect of the physical properties of nanoparticles on the biological interaction between the material and the human body requires to be further studied to ensure the stability and operability of the nanovaccine design process.

4. Perspective and conclusion

CTAs are a large protein family expressed in malignant tumors and male testicular tissues, possessing certain immunogenicity due to the blood-testis barrier, and may stimulate humoral and cellular immunity in patients with malignancies. Members of the same CTA subfamily usually share a similar structure, co-expression pattern and biofunctions in tumors. Exploration of the structural characteristics, biological functions and immunogenicity of CTA families is helpful for developing antitumor treatment strategies. The MAGE, SSX, GAGE, XAGE and PAGE families are all X chromosome-linked CTA families and are activated in various malignant tumors. Co-expression pattern and structural homology shared between subfamily members render them optimal targets for tumor diagnosis and treatment. So far, therapeutic strategies targeting CTA have gained increasing attention to treat tumors either used independently or in combination with other treatments (148). CTAs are usually used as cancer vaccine targets, yet clinical translation is still limited in spite of promising results achieved at the preclinical stage. The underlying reasons may be attributed to the heterogenous expression in tumors and restricted expression of certain CTAs in normal tissues. Thus, the co-expression pattern and structural homology of CTA subfamily members should be taken into account when designing CTA-based therapies.

Cancer vaccines represent a promising therapeutic modality with several advantages. DNA, mRNA and peptide-based cancer vaccines are commonly-used vaccination forms with their own merits and drawbacks. During vaccination, low immunogenicity is generally observed, leading to limited anticancer efficacy. Furthermore, the immunosuppressive TME also hinders the immune response induced by a specific antigen. In view of this, nanomaterial-derived delivery systems may be applied to realize co-delivery of multiple antigens, as well as immune modulators to reverse the immunosuppressive TME. Since antigen identification has long been attributed to be the main reason for the low efficiency of the cancer vaccination cascade, resulting in poor performance in clinical trials, CTA subfamilies should be considered optimal candidates for designing cancer vaccines. In particular, CTA-based nanovaccines will become an attractive strategy for enhancing the antitumor effects of cancer vaccines in the future. At the same time, attention should also be paid to maintaining the balance between the complexity and composition of the nanostructure and the therapeutic effect, to minimize the toxicity of nanomaterials and maximize the therapeutic efficacy.

Availability of data and materials

Not applicable.

Authors' contributions

Conceptualization, FFC; methodology, SNR and ZYZ; analysis and interpretation of data, MYL and DRW; writing-original draft preparation, SNR and ZYZ; writing-review and editing, SNR; visualization, RJG; design and funding acquisition, XDF and FFC. All authors have read and agreed to the published version of the manuscript. Data authentication is not applicable.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.


Not applicable.


The present study was supported by the National Key Research and Development Program (grant nos. 2021YFC2400600 and 2021YFC2400603), the National Natural Science Foundation of China (grant no. 32271446), Program of Health Department of Jilin Province (grant nos. 2022SCZ26, 2022JC075 and 2022LC121), Norman Bethune Program of Jilin University (grant nos. 2022B21 and 2022B37), the China Postdoctoral Science Foundation (grant no. 2022TQ0118) and the Natural Science Foundation of Jilin Province (grant nos. YDZJ202101ZYTS024 and YDZJ202301ZYTS427).



Gibbs ZA and Whitehurst AW: Emerging contributions of cancer/testis antigens to neoplastic behaviors. Trends Cancer. 4:701–712. 2018.


Saxena M, van der Burg SH, Melief CJM and Bhardwaj N: Therapeutic cancer vaccines. Nat Rev Cancer. 21:360–378. 2021.


Florke Gee RR, Chen H, Lee AK, Daly CA, Wilander BA, Fon Tacer K and Potts PR: Emerging roles of the MAGE protein family in stress response pathways. J Biol Chem. 295:16121–16155. 2020.


Lian Y, Meng L, Ding P and Sang M: Epigenetic regulation of MAGE family in human cancer progression-DNA methylation, histone modification, and non-coding RNAs. Clin Epigenetics. 10:1152018.


Marchand M, van Baren N, Weynants P, Brichard V, Dréno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, et al: Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer. 80:219–230. 1999.


Parvizpour S, Razmara J, Pourseif MM and Omidi Y: In silico design of a triple-negative breast cancer vaccine by targeting cancer testis antigens. Bioimpacts. 9:45–56. 2019.


Vansteenkiste JF, Cho BC, Vanakesa T, De Pas T, Zielinski M, Kim MS, Jassem J, Yoshimura M, Dahabreh J, Nakayama H, et al: Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 17:822–835. 2016.


Miao L, Zhang Y and Huang L: mRNA vaccine for cancer immunotherapy. Mol Cancer. 20:412021.


Sahin U and Türeci O: Personalized vaccines for cancer immunotherapy. Science. 359:1355–1360. 2018.


Chen F, Wang Y, Gao J, Saeed M, Li T, Wang W and Yu H: Nanobiomaterial-based vaccination immunotherapy of cancer. Biomaterials. 270:1207092021.


Polla Ravi S, Shamiya Y, Chakraborty A, Elias C and Paul A: Biomaterials, biological molecules, and polymers in developing vaccines. Trends Pharmacol Sci. 42:813–828. 2021.


Xiao L, Huang Y, Yang Y, Miao Z, Zhu J, Zhong M, Feng C, Tang W, Zhou J, Wang L, et al: Biomimetic cytomembrane nanovaccines prevent breast cancer development in the long term. Nanoscale. 13:3594–3601. 2021.


Verma P, Biswas S, Yadav N, Khatri A, Siddiqui H, Panda JJ, Rawat BS, Tailor P and Chauhan VS: Delivery of a cancer-testis antigen-derived peptide using conformationally restricted dipeptide-based self-assembled nanotubes. Mol Pharm. 18:3832–3842. 2021.


Huang W, Zhang Q, Li W, Yuan M, Zhou J, Hua L, Chen Y, Ye C and Ma Y: Development of novel nanoantibiotics using an outer membrane vesicle-based drug efflux mechanism. J Control Release. 317:1–22. 2020.


Jian W, Li X, Kang J, Lei Y, Bai Y and Xue Y: Antitumor effect of recombinant Mycobacterium smegmatis expressing MAGEA3 and SSX2 fusion proteins. Exp Ther Med. 16:2160–2166. 2018.


Sebastian M, Schröder A, Scheel B, Hong HS, Muth A, von Boehmer L, Zippelius A, Mayer F, Reck M, Atanackovic D, et al: A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer. Cancer Immunol Immunother. 68:799–812. 2019.


Neek M, Tucker JA, Kim TI, Molino NM, Nelson EL and Wang SW: Co-delivery of human cancer-testis antigens with adjuvant in protein nanoparticles induces higher cell-mediated immune responses. Biomaterials. 156:194–203. 2018.


van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A and Boon T: A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. J Immunol. 178:2617–2621. 2007.


van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A and Boon T: A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 254:1643–1647. 1991.


Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T and Lucas S: An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 61:5544–5551. 2001.


Barker PA and Salehi A: The MAGE proteins: Emerging roles in cell cycle progression, apoptosis, and neurogenetic disease. J Neurosci Res. 67:705–712. 2002.


Lee AK and Potts PR: A comprehensive guide to the MAGE family of ubiquitin ligases. J Mol Biol. 429:1114–1142. 2017.


Simpson AJG, Caballero OL, Jungbluth A, Chen YT and Old LJ: Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 5:615–625. 2005.


De Plaen E, Arden K, Traversari C, Gaforio JJ, Szikora JP, De Smet C, Brasseur F, van der Bruggen P, Lethé B, Lurquin C, et al: Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics. 40:360–369. 1994.


Rogner UC, Wilke K, Steck E, Korn B and Poustka A: The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28. Genomics. 29:725–731. 1995.


Li S, Shi X, Li J and Zhou X: Pathogenicity of the MAGE family. Oncol Lett. 22:8442021.


van den Elsen GA, Tobben L, Ahmed AI, Verkes RJ, Kramers C, Marijnissen RM, Olde Rikkert MG and van der Marck MA: Effects of tetrahydrocannabinol on balance and gait in patients with dementia: A randomised controlled crossover trial. J Psychopharmacol. 31:184–191. 2017.


Kerkar SP, Wang ZF, Lasota J, Park T, Patel K, Groh E, Rosenberg SA and Miettinen MM: MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases. J Immunother. 39:181–187. 2016.


Fon Tacer K, Montoya MC, Oatley MJ, Lord T, Oatley JM, Klein J, Ravichandran R, Tillman H, Kim M, Connelly JP, et al: MAGE cancer-testis antigens protect the mammalian germline under environmental stress. Sci Adv. 5:eaav48322019.


Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, Chen ZJ, Billadeau DD, Rosen MK and Potts PR: Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. Cell. 152:1051–1064. 2013.


Liu S, Sang M, Xu Y, Gu L, Liu F and Shan B: Expression of MAGE-A1, -A9, -A11 in laryngeal squamous cell carcinoma and their prognostic significance: A retrospective clinical study. Acta Otolaryngol. 136:506–513. 2016.


Hou SY, Sang MX, Geng CZ, Liu WH, Lü WH, Xu YY and Shan BE: Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression mechanism. Arch Med Res. 45:44–51. 2014.


Guo L, Sang M, Liu Q, Fan X, Zhang X and Shan B: The expression and clinical significance of melanoma-associated antigen-A1, -A3 and -A11 in glioma. Oncol Lett. 6:55–62. 2013.


De Smet C, Loriot A and Boon T: Promoter-dependent mechanism leading to selective hypomethylation within the 5' region of gene MAGE-A1 in tumor cells. Mol Cell Biol. 24:4781–4790. 2004.


Wischnewski F, Pantel K and Schwarzenbach H: Promoter demethylation and histone acetylation mediate gene expression of MAGE-A1, -A2, -A3, and -A12 in human cancer cells. Mol Cancer Res. 4:339–349. 2006.


Laiseca JE, Ladelfa MF, Cotignola J, Peche LY, Pascucci FA, Castaño BA, Galigniana MD, Schneider C and Monte M: Functional interaction between co-expressed MAGE-A proteins. PLoS One. 12:e01783702017.


Mahmoud AM: Cancer testis antigens as immunogenic and oncogenic targets in breast cancer. Immunotherapy. 10:769–778. 2018.


Salmaninejad A, Zamani MR, Pourvahedi M, Golchehre Z, Hosseini Bereshneh A and Rezaei N: Cancer/testis antigens: Expression, regulation, tumor invasion, and use in immunotherapy of cancers. Immunol Invest. 45:619–640. 2016.


Õunap K, Kurg K, Võsa L, Maiväli Ü, Teras M, Planken A, Ustav M and Kurg R: Antibody response against cancer-testis antigens MAGEA4 and MAGEA10 in patients with melanoma. Oncol Lett. 16:211–218. 2018.


Djureinovic D, Dodig-Crnković T, Hellström C, Holgersson G, Bergqvist M, Mattsson JSM, Pontén F, Ståhle E, Schwenk JM and Micke P: Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer. Lung Cancer. 125:157–163. 2018.


Mischo A, Kubuschok B, Ertan K, Preuss KD, Romeike B, Regitz E, Schormann C, de Bruijn D, Wadle A, Neumann F, et al: Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer. Int J Cancer. 118:696–703. 2006.


Zang C, Zhao Y, Qin L, Liu G, Sun J, Li K, Zhao Y, Sheng S, Zhang H, He N, et al: Distinct tumour antigen-specific T-cell immune response profiles at different hepatocellular carcinoma stages. BMC Cancer. 21:10072021.


Connerotte T, Van Pel A, Godelaine D, Tartour E, Schuler-Thurner B, Lucas S, Thielemans K, Schuler G and Coulie PG: Functions of Anti-MAGE T-cells induced in melanoma patients under different vaccination modalities. Cancer Res. 68:3931–3940. 2008.


Huang LQ, Brasseur F, Serrano A, De Plaen E, van der Bruggen P, Boon T and Van Pel A: Cytolytic T lymphocytes recognize an antigen encoded by MAGE-A10 on a human melanoma. J Immunol. 162:6849–6854. 1999.


Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, Ritter G, Simpson AJ, Chen YT, Old LJ and Altorki NK: Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res. 11:8055–8062. 2005.


Zhang S, Zhai X, Wang G, Feng J, Zhu H, Xu L, Mao G and Huang J: High expression of MAGE-A9 in tumor and stromal cells of non-small cell lung cancer was correlated with patient poor survival. Int J Clin Exp Patho. 8:541–550. 2015.


Qi Y, Cao KX, Xing FC, Zhang CY, Huang Q, Wu K, Wen FB, Zhao S and Li X: High expression of MAGE-A9 is associated with unfavorable survival in esophageal squamous cell carcinoma. Oncol Lett. 14:3415–3420. 2017.


Sang M, Wang L, Ding C, Zhou X, Wang B, Wang L, Lian Y and Shan B: Melanoma-associated antigen genes-an update. Cancer Lett. 302:85–90. 2011.


Doyle JM, Gao J, Wang J, Yang M and Potts PR: MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol Cell. 39:963–974. 2010.


Xiao TZ, Suh Y and Longley BJ: MAGE proteins regulate KRAB zinc finger transcription factors and KAP1 E3 ligase activity. Arch Biochem Biophys. 563:136–144. 2014.


Su S, Chen X, Geng J, Minges JT, Grossman G and Wilson EM: Melanoma antigen-A11 regulates substrate-specificity of Skp2-mediated protein degradation. Mol Cell Endocrinol. 439:1–9. 2017.


Cui J, Wang L, Zhong W, Chen Z, Chen J, Yang H and Liu G: Development and validation of epigenetic signature predict survival for patients with laryngeal squamous cell carcinoma. DNA Cell Biol. 40:247–264. 2021.


Cui J, Chen Y, Ou Y, Liu G, Wen Q, Zhu W, Liang L, Chen Z, Yang H, Wang L and Wei M: Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer. Clin Immunol. 240:1090452022.


Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cadwell K, Cecconi F, Choi AMK, et al: Autophagy in major human diseases. EMBO J. 40:e1088632021.


Ravichandran R, Kodali K, Peng J and Potts PR: Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient availability. EMBO Rep. 20:e473522019.


Güre AO, Wei IJ, Old LJ and Chen YT: The SSX gene family: Characterization of 9 complete genes. Int J Cancer. 101:448–453. 2002.


Crew AJ, Clark J, Fisher C, Gill S, Grimer R, Chand A, Shipley J, Gusterson BA and Cooper CS: Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J. 14:2333–2340. 1995.


Skytting B, Nilsson G, Brodin B, Xie Y, Lundeberg J, Uhlén M and Larsson O: A novel fusion gene, SYT-SSX4, in synovial sarcoma. J Natl Cancer Inst. 91:974–975. 1999.


Feng X, Huang YL, Zhang Z, Wang N, Yao Q, Pang LJ, Li F and Qi Y: The role of SYT-SSX fusion gene in tumorigenesis of synovial sarcoma. Pathol Res Pract. 222:1534162021.


Fligman I, Lonardo F, Jhanwar SC, Gerald WL, Woodruff J and Ladanyi M: Molecular diagnosis of synovial sarcoma and characterization of a variant SYT-SSX2 fusion transcript. Am J Pathol. 147:1592–1599. 1995.


dos Santos NR, Torensma R, de Vries TJ, Schreurs MW, de Bruijn DR, Kater-Baats E, Ruiter DJ, Adema GJ, van Muijen GN and van Kessel AG: Heterogeneous expression of the SSX cancer/testis antigens in human melanoma lesions and cell lines. Cancer Res. 60:1654–1662. 2000.


Lim FL, Soulez M, Koczan D, Thiesen HJ and Knight JC: A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas. Oncogene. 17:2013–2018. 1998.


dos Santos NR, de Bruijn DR, Kater-Baats E, Otte AP and van Kessel AG: Delineation of the protein domains responsible for SYT, SSX, and SYT-SSX nuclear localization. Exp Cell Res. 256:192–202. 2000.


Cronwright G, Le Blanc K, Götherström C, Darcy P, Ehnman M and Brodin B: Cancer/testis antigen expression in human mesenchymal stem cells: Down-regulation of SSX impairs cell migration and matrix metalloproteinase 2 expression. Cancer Res. 65:2207–2215. 2005.


Anderson WJ, Maclean FM, Acosta AM and Hirsch MS: Expression of the C-terminal region of the SSX protein is a useful diagnostic biomarker for spermatocytic tumour. Histopathology. 79:700–707. 2021.


Johansen S and Gjerstorff MF: Interaction between polycomb and SSX proteins in pericentromeric heterochromatin function and its implication in cancer. Cells. 9:2262020.


Wei R, Dean DC, Thanindratarn P, Hornicek FJ, Guo W and Duan ZF: Cancer testis antigens in sarcoma: Expression, function and immunotherapeutic application. Cancer Lett. 479:54–60. 2020.


Türeci O, Chen YT, Sahin U, Güre AO, Zwick C, Villena C, Tsang S, Seitz G, Old LJ and Pfreundschuh M: Expression of SSX genes in human tumors. Int J Cancer. 77:19–23. 1998.


Jones PA and Gonzalgo ML: Altered DNA methylation and genome instability: A new pathway to cancer? Proc Natl Acad Sci USA. 94:2103–2105. 1997.


Atanackovic D, Arfsten J, Cao Y, Gnjatic S, Schnieders F, Bartels K, Schilling G, Faltz C, Wolschke C, Dierlamm J, et al: Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Blood. 109:1103–1112. 2007.


Neumann F, Kubuschok B, Ertan K, Schormann C, Stevanovic S, Preuss KD, Schmidt W and Pfreundschuh M: A peptide epitope derived from the cancer testis antigen HOM-MEL-40/SSX2 capable of inducing CD4+ and CD8+ T-cell as well as B-cell responses. Cancer Immunol Immunother. 60:1333–1346. 2011.


Hasegawa K, Koizumi F, Noguchi Y, Hongo A, Mizutani Y, Kodama J, Hiramatsu Y and Nakayama E: SSX expression in gynecological cancers and antibody response in patients. Cancer Immun. 4:162004.


Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, Mellman I, Prindiville SA, Viner JL, Weiner LM and Matrisian LM: The prioritization of cancer antigens: A national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 15:5323–5337. 2009.


McBride MJ, Pulice JL, Beird HC, Ingram DR, D'Avino AR, Shern JF, Charville GW, Hornick JL, Nakayama RT, Garcia-Rivera EM, et al: The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma. Cancer Cell. 33:1128–1141.e7. 2018.


Banito A, Li X, Laporte AN, Roe JS, Sanchez-Vega F, Huang CH, Dancsok AR, Hatzi K, Chen CC, Tschaharganeh DF, et al: The SS18-SSX oncoprotein hijacks KDM2B-PRC1 1 to drive synovial sarcoma. Cancer Cell. 33:527–541.e8. 2018.


Déjardin J: Switching between epigenetic states at pericentromeric heterochromatin. Trends Genet. 31:661–672. 2015.


Schwartz YB, Kahn TG, Nix DA, Li XY, Bourgon R, Biggin M and Pirrotta V: Genome-wide analysis of polycomb targets in drosophila melanogaster. Nat Genet. 38:700–705. 2006.


Barco R, Garcia CB and Eid JE: The synovial sarcoma-associated SYT-SSX2 oncogene antagonizes the polycomb complex protein Bmi1. PLoS One. 4:e50602009.


Wang J, Wang H, Hou W, Liu H, Zou Y, Zhang H, Hou L, McNutt MA and Zhang B: Subnuclear distribution of SSX regulates its function. Mol Cell Biochem. 381:17–29. 2013.


Gjerstorff MF and Ditzel HJ: An overview of the GAGE cancer/testis antigen family with the inclusion of newly identified members. Tissue Antigens. 71:187–192. 2008.


Gjerstorff MF, Johansen LE, Nielsen O, Kock K and Ditzel HJ: Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy. Br J Cancer. 94:1864–1873. 2006.


Gjerstorff MF, Kock K, Nielsen O and Ditzel HJ: MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development. Hum Reprod. 22:953–960. 2007.


Gordeeva O: Cancer-testis antigens: Unique cancer stem cell biomarkers and targets for cancer therapy. Semin Cancer Biol. 53:75–89. 2018.


Tabatabaei Yazdi SA, Safaei M, Gholamin M, Abdollahi A, Nili F, Jabbari Nooghabi M, Anvari K and Mojarrad M: Expression and prognostic significance of cancer/testis antigens, MAGE-E1, GAGE, and SOX-6, in glioblastoma: An immunohistochemistry evaluation. Iran J Pathol. 16:128–136. 2021.


Götte K, Usener D, Riedel F, Hörmann K, Schadendorf D and Eichmüller S: Tumor-associated antigens as possible targets for immune therapy in head and neck cancer: Comparative mRNA expression analysis of RAGE and GAGE genes. Acta Otolaryngol. 122:546–552. 2002.


Chao NX, Li LZ, Luo GR, Zhong WG, Huang RS, Fan R and Zhao FL: Cancer-testis antigen GAGE-1 expression and serum immunoreactivity in hepatocellular carcinoma. Niger J Clin Pract. 21:1361–1367. 2018.


Zhang SQ, Zhou XL, Yu H and Yu YH: Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines. BMC Cancer. 10:1632010.


Kutilin DS: Regulation of gene expression of cancer/testis antigens in colorectal cancer patients. Mol Biol. 54:520–534. 2020.


Zhang R, Ma L, Li W, Zhou S and Xu S: Diagnostic value of multiple tumor-associated autoantibodies in lung cancer. Onco Targets Ther. 12:457–469. 2019.


Ghafouri-Fard S, Seifi-Alan M, Shamsi R and Esfandiary A: Immunotherapy in multiple myeloma using cancer-testis antigens. Iran J Cancer Prev. 8:e37552015.


Melo DH, Mamede RCM, Neder L, Silva WA Jr, Barros-Filho MC, Kowalski LP, Pinto CAL, Zago MA, Figueiredo DLA and Jungbluth AA: Expression of cancer/testis antigens MAGE-A, MAGE-C1, GAGE and CTAG1B in benign and malignant thyroid diseases. Oncol Lett. 14:6485–6496. 2017.


Sun F, Chan E, Wu Z, Yang X, Marquez VE and Yu Q: Combinatorial pharmacologic approaches target EZH2-mediated gene repression in breast cancer cells. Mol Cancer Ther. 8:3191–3202. 2009.


Bazhin AV, Wiedemann N, Schnölzer M, Schadendorf D and Eichmüller SB: Expression of GAGE family proteins in malignant melanoma. Cancer Lett. 251:258–267. 2007.


Gjerstorff MF, Rösner HI, Pedersen CB, Greve KB, Schmidt S, Wilson KL, Mollenhauer J, Besir H, Poulsen FM, Møllegaard NE and Ditzel HJ: GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL). PLoS One. 7:e458192012.


Kular RK, Yehiely F, Kotlo KU, Cilensek ZM, Bedi R and Deiss LP: GAGE, an antiapoptotic protein binds and modulates the expression of nucleophosmin/B23 and interferon regulatory factor 1. J Interferon Cytokine Res. 29:645–655. 2009.


Nin DS, Wujanto C, Tan TZ, Lim D, Damen JMA, Wu KY, Dai ZM, Lee ZW, Idres SB, Leong YH, et al: GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility. Cell Rep. 36:1096212021.


Zendman AJW, Van Kraats AA, Weidle UH, Ruiter DJ and Van Muijen GN: The XAGE family of cancer/testis-associated genes: alignment and expression profile in normal tissues, melanoma lesions and Ewing's sarcoma. Int J Cancer. 99:361–369. 2002.


Xie C and Wang GM: XAGE-1b cancer/testis antigen is a potential target for immunotherapy in prostate cancer. Urol Int. 94:354–362. 2015.


Nakagawa K, Noguchi Y, Uenaka A, Sato S, Okumura H, Tanaka M, Shimono M, Ali Eldib AM, Ono T, Ohara N, et al: XAGE-1 expression in non-small cell lung cancer and antibody response in patients. Clin Cancer Res. 11:5496–5503. 2005.


Pan Z, Tang B, Hou Z, Zhang J, Liu H, Yang Y, Huang G, Yang Y and Zhou W: XAGE-1b expression is associated with the diagnosis and early recurrence of hepatocellular carcinoma. Mol Clin Oncol. 2:1155–1159. 2014.


Gong L, Peng J, Cui Z, Chen P, Han H, Zhang D and Leng X: Hepatocellular carcinoma patients highly and specifically expressing XAGE-1 exhibit prolonged survival. Oncol Lett. 1:1083–1088. 2010.


Koizumi F, Noguchi Y, Saika T, Nakagawa K, Sato S, Eldib AM, Nasu Y, Kumon H and Nakayama E: XAGE-1 mRNA expression in prostate cancer and antibody response in patients. Microbiol Immunol. 49:471–476. 2005.


Mori M, Funakoshi T, Kameyama K, Kawakami Y, Sato E, Nakayama E, Amagai M and Tanese K: Lack of XAGE-1b and NY-ESO-1 in metastatic lymph nodes may predict the potential survival of stage III melanoma patients. J Dermatol. 44:671–680. 2017.


Tarek MM, Shafei AE, Ali MA and Mansour MM: Computational prediction of vaccine potential epitopes and 3-dimensional structure of XAGE-1b for non-small cell lung cancer immunotherapy. Biomed J. 41:118–128. 2018.


Talebian Yazdi M, Loof NM, Franken KL, Taube C, Oostendorp J, Hiemstra PS, Welters MJ and van der Burg SH: Local and systemic XAGE-1b-specific immunity in patients with lung adenocarcinoma. Cancer Immunol Immunother. 64:1109–1121. 2015.


Zhou B, Li T, Liu Y and Zhu N: Preliminary study on XAGE-1b gene and its mechanism for promoting tumor cell growth. Biomed Rep. 1:567–572. 2013.


Brinkmann U, Vasmatzis G, Lee B, Yerushalmi N, Essand M and Pastan I: PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus. Proc Natl Acad Sci USA. 95:10757–10762. 1998.


Kulkarni P, Dunker AK, Weninger K and Orban J: Prostate-associated gene 4 (PAGE4), an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer. Asian J Androl. 18:695–703. 2016.


Suyama T, Shiraishi T, Zeng Y, Yu W, Parekh N, Vessella RL, Luo J, Getzenberg RH and Kulkarni P: Expression of cancer/testis antigens in prostate cancer is associated with disease progression. Prostate. 70:1778–1787. 2010.


Zeng Y, Gao D, Kim JJ, Shiraishi T, Terada N, Kakehi Y, Kong C, Getzenberg RH and Kulkarni P: Prostate-associated gene 4 (PAGE4) protects cells against stress by elevating p21 and suppressing reactive oxygen species production. Am J Clin Exp Urol. 1:39–52. 2013.


Yilmaz-Ozcan S, Sade A, Kucukkaraduman B, Kaygusuz Y, Senses KM, Banerjee S and Gure AO: Epigenetic mechanisms underlying the dynamic expression of cancer-testis genes, PAGE2, -2B and SPANX-B, during mesenchymal-to-epithelial transition. PLoS One. 9:e1079052014.


Hellman M, Tossavainen H, Rappu P, Heino J and Permi P: Characterization of intrinsically disordered prostate associated gene (PAGE5) at single residue resolution by NMR spectroscopy. PLoS One. 6:e266332011.


Salgia R, Jolly MK, Dorff T, Lau C, Weninger K, Orban J and Kulkarni P: Prostate-associated gene 4 (PAGE4): Leveraging the conformational dynamics of a dancing protein cloud as a therapeutic target. J Clin Med. 7:1562018.


Uversky VN: Dancing protein clouds: The strange biology and chaotic physics of intrinsically disordered proteins. J Biol Chem. 291:6681–6688. 2016.


Monika FJ, Simon I, Friedrich P and Tompa P: Preformed structural elements feature in partner recognition by intrinsically unstructured proteins. Biophys J. 88:560a2005.


Sampson N, Ruiz C, Zenzmaier C, Bubendorf L and Berger P: PAGE4 positivity is associated with attenuated AR signaling and predicts patient survival in hormone-naive prostate cancer. Am J Pathol. 181:1443–1454. 2012.


Lv C, Fu S, Dong Q, Yu Z, Zhang G, Kong C, Fu C and Zeng Y: PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway. J Exp Clin Cancer Res. 38:242019.


Rajagopalan K, Qiu R, Mooney SM, Rao S, Shiraishi T, Sacho E, Huang H, Shapiro E, Weninger KR and Kulkarni P: The stress-response protein prostate-associated gene 4, interacts with c-Jun and potentiates its transactivation. Biochim Biophys Acta. 1842:154–163. 2014.


Tavakoli Koudehi A, Mahjoubi B, Mirzaei R, Shabani S and Mahjoubi F: AKAP4, SPAG9 and NY-ESO-1 in Iranian colorectal cancer patients as probable diagnostic and prognostic biomarkers. Asian Pac J Cancer Prev. 19:463–469. 2018.


Chen YT, Scanlan MJ, Sahin U, Türeci O, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M and Old LJ: A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA. 94:1914–1918. 1997.


Raza A, Merhi M, Inchakalody VP, Krishnankutty R, Relecom A, Uddin S and Dermime S: Unleashing the immune response to NY-ESO-1 cancer testis antigen as a potential target for cancer immunotherapy. J Transl Med. 18:1402020.


Smith SM and Iwenofu OH: NY-ESO-1: A promising cancer testis antigen for sarcoma immunotherapy and diagnosis. Chin Clin Oncol. 7:442018.


Pollack SM: The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients. Expert Rev Vaccines. 17:107–114. 2018.


Jo U, Roh J, Song MJ, Cho KJ, Kim W and Song JS: NY-ESO-1 as a diagnostic and prognostic marker for myxoid liposarcoma. Am J Transl Res. 14:1268–1278. 2022.


Hashimoto K, Nishimura S, Ito T, Oka N, Kakinoki R and Akagi M: Clinicopathological assessment of cancer/testis antigens NY-ESO-1 and MAGE-A4 in osteosarcoma. Eur J Histochem. 66:33772022.


Nagata Y, Kageyama S, Ishikawa T, Kokura S, Okayama T, Abe T, Murakami M, Otsuka K, Ariyoshi T, Kojima T, et al: Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy. Cancer Immunol Immunother. 71:2743–2755. 2022.


Čeprnja T, Mrklić I, Perić Balja M, Marušić Z, Blažićević V, Spagnoli GC, Juretić A, Čapkun V, Tečić Vuger A, Vrdoljak E and Tomić S: Prognostic significance of lymphocyte infiltrate localization in triple-negative breast cancer. J Pers Med. 12:9412022.


Liu MY, Su H, Huang HL and Chen JQ: Cancer stem-like cells with increased expression of NY-ESO-1 initiate breast cancer metastasis. Oncol Lett. 18:3664–3672. 2019.


van Rhee F, Szmania SM, Zhan F, Gupta SK, Pomtree M, Lin P, Batchu RB, Moreno A, Spagnoli G, Shaughnessy J and Tricot G: NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood. 105:3939–3944. 2005.


Iura K, Kohashi K, Hotokebuchi Y, Ishii T, Maekawa A, Yamada Y, Yamamoto H, Iwamoto Y and Oda Y: Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma. J Pathol Clin Res. 1:144–159. 2015.


Giavina-Bianchi M, Giavina-Bianchi P, Sotto MN, Muzikansky A, Kalil J, Festa-Neto C and Duncan LM: Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma. J Immunol Res. 2015:7613782015.


Wang H, Chen D, Wang R, Quan W, Xia D, Mei J, Xu J and Liu C: NY-ESO-1 expression in solid tumors predicts prognosis: A systematic review and meta-analysis. Medicine (Baltimore). 98:e179902019.


Gnjatic S, Nishikawa H, Jungbluth AA, Güre AO, Ritter G, Jäger E, Knuth A, Chen YT and Old LJ: NY-ESO-1: review of an immunogenic tumor antigen. Adv Cancer Res. 95:1–30. 2006.


Thomas R, Al-Khadairi G, Roelands J, et al: NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives. Frontiers in immunology. 9:9472018.


Astaneh M, Dashti S and Esfahani ZT: Humoral immune responses against cancer-testis antigens in human malignancies. Hum Antibodies. 27:237–240. 2019.


Jäger E, Gnjatic S, Nagata Y, Stockert E, Jäger D, Karbach J, Neumann A, Rieckenberg J, Chen YT, Ritter G, et al: Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers. Proc Natl Acad Sci USA. 97:12198–12203. 2000.


Jäger E, Nagata Y, Gnjatic S, Wada H, Stockert E, Karbach J, Dunbar PR, Lee SY, Jungbluth A, Jäger D, et al: Monitoring CD8 T cell responses to NY-ESO-1: Correlation of humoral and cellular immune responses. Proc Natl Acad Sci USA. 97:4760–4765. 2000.


Barrow C, Browning J, MacGregor D, Davis ID, Sturrock S, Jungbluth AA and Cebon J: Tumor antigen expression in melanoma varies according to antigen and stage. Clin Cancer Res. 12:764–771. 2006.


Li F, Zhao F, Li M, Pan M, Shi F, Xu H, Zheng D, Wang L and Dou J: Decreasing New York esophageal squamous cell carcinoma 1 expression inhibits multiple myeloma growth and osteolytic lesions. J Cell Physiol. 235:2183–2194. 2020.


Wang H, Xia Y, Yu J, Guan H, Wu Z, Ban D and Wang M: Expression of New York esophageal squamous cell carcinoma 1 and its association with Foxp3 and indoleamine-2,3-dioxygenase in microenvironment of nonsmall cell lung cancer. HLA. 94:39–48. 2019.


Ko TY, Kim JI and Lee SH: Relationship between cancer stem cell marker CD133 and cancer germline antigen genes in NCI-H292 lung cancer cells. Korean J Thorac Cardiovasc Surg. 53:22–27. 2020.


Gong W, Hoffmann JM, Stock S, Wang L, Liu Y, Schubert ML, Neuber B, Hückelhoven-Krauss A, Gern U, Schmitt A, et al: Comparison of IL-2 vs IL-7/IL-15 for the generation of NY-ESO-1-specific T cells. Cancer Immunol Immunother. 68:1195–1209. 2019.


Hirayama M, Tomita Y, Yuno A, Tsukamoto H, Senju S, Imamura Y, Sayem MA, Irie A, Yoshitake Y, Fukuma D, et al: An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs. Oncoimmunology. 5:e11233682016.


Hayashi R, Nagato T, Kumai T, Ohara K, Ohara M, Ohkuri T, Hirata-Nozaki Y, Harabuchi S, Kosaka A, Nagata M, et al: Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma. Oncoimmunology. 10:18565452020.


Minhas V, Kumar R, Moitra T, Singh R, Panda AK and Gupta SK: Immunogenicity and contraceptive efficacy of recombinant fusion protein encompassing Sp17 spermatozoa-specific protein and GnRH: Relevance of adjuvants and microparticles based delivery to minimize number of injections. Am J Reprod Immunol. 83:e132182020.


Taheri-Anganeh M, Savardashtaki A, Vafadar A, Movahedpour A, Shabaninejad Z, Maleksabet A, Amiri A, Ghasemi Y and Irajie C: In silico design and evaluation of PRAME+FliCΔD2D3 as a new breast cancer vaccine candidate. Iran J Med Sci. 46:52–60. 2021.


Matteo M, Greco P, Levi Setti PE, Morenghi E, De Rosario F, Massenzio F, Albani E, Totaro P and Liso A: Preliminary evidence for high anti-PLAC1 antibody levels in infertile patients with repeated unexplained implantation failure. Placenta. 34:335–339. 2013.


Fan C, Qu H, Wang X, Sobhani N, Wang L, Liu S, Xiong W, Zeng Z and Li Y: Cancer/testis antigens: From serology to mRNA cancer vaccine. Semin Cancer Biol. 76:218–231. 2021.


Kono K, Mizukami Y, Daigo Y, Takano A, Masuda K, Yoshida K, Tsunoda T, Kawaguchi Y, Nakamura Y and Fujii H: Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer. Cancer Sci. 100:1502–1509. 2009.


Lopes A, Vandermeulen G and Préat V: Cancer DNA vaccines: Current preclinical and clinical developments and future perspectives. J Exp Clin Cancer Res. 38:1462019.


Herrada AA, Rojas-Colonelli N, González-Figueroa P, Roco J, Oyarce C, Ligtenberg MA and Lladser A: Harnessing DNA-induced immune responses for improving cancer vaccines. Hum Vaccin Immunother. 8:1682–1693. 2012.


Rezaei T, Davoudian E, Khalili S, Amini M, Hejazi M, de la Guardia M and Mokhtarzadeh A: Strategies in DNA vaccine for melanoma cancer. Pigment Cell Melanoma Res. 34:869–891. 2021.


Wu Y, Sang M, Liu F, Zhang J, Li W, Li Z, Gu L, Zheng Y, Li J and Shan B: Epigenetic modulation combined with PD-1/PD-L1 blockade enhances immunotherapy based on MAGE-A11 antigen-specific CD8+T cells against esophageal carcinoma. Carcinogenesis. 41:894–903. 2020.


Jahanafrooz Z, Baradaran B, Mosafer J, Hashemzaei M, Rezaei T, Mokhtarzadeh A and Hamblin MR: Comparison of DNA and mRNA vaccines against cancer. Drug Discov Today. 25:552–560. 2020.


Heine A, Juranek S and Brossart P: Clinical and immunological effects of mRNA vaccines in malignant diseases. Mol Cancer. 20:522021.


Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, Baum A, Pascal K, Quandt J, Maurus D, et al: COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 586:594–599. 2020.


Liu W, Tang H, Li L, Wang X, Yu Z and Li J: Peptide-based therapeutic cancer vaccine: Current trends in clinical application. Cell Prolif. 54:e130252021.


Nelde A, Rammensee HG and Walz JS: The peptide vaccine of the future. Mol Cell Proteomics. 20:1000222021.


Iinuma H, Fukushima R, Inaba T, Tamura J, Inoue T, Ogawa E, Horikawa M, Ikeda Y, Matsutani N, Takeda K, et al: Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients. J Transl Med. 12:842014.


Kono K, Iinuma H, Akutsu Y, Tanaka H, Hayashi N, Uchikado Y, Noguchi T, Fujii H, Okinaka K, Fukushima R, et al: Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. J Transl Med. 10:1412012.


Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, et al: gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 364:2119–2127. 2011.


Suzuki H, Fukuhara M, Yamaura T, Mutoh S, Okabe N, Yaginuma H, Hasegawa T, Yonechi A, Osugi J, Hoshino M, et al: Multiple therapeutic peptide vaccines consisting of combined novel cancer testis antigens and anti-angiogenic peptides for patients with non-small cell lung cancer. J Transl Med. 11:972013.


Kotsakis A, Papadimitraki E, Vetsika EK, Aggouraki D, Dermitzaki EK, Hatzidaki D, Kentepozidis N, Mavroudis D and Georgoulias V: A phase II trial evaluating the clinical and immunologic response of HLA-A2(+) non-small cell lung cancer patients vaccinated with an hTERT cryptic peptide. Lung Cancer. 86:59–66. 2014.


Yoshitake Y, Fukuma D, Yuno A, Hirayama M, Nakayama H, Tanaka T, Nagata M, Takamune Y, Kawahara K, Nakagawa Y, et al: Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS. Clin Cancer Res. 21:312–321. 2015.


Okuyama R, Aruga A, Hatori T, Takeda K and Yamamoto M: Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients. Oncoimmunology. 2:e270102013.


Smith HA, Rekoske BT and McNeel DG: DNA vaccines encoding altered peptide ligands for SSX2 enhance epitope-specific CD8+ T-cell immune responses. Vaccine. 32:1707–1715. 2014.


Li L and Petrovsky N: Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines. 15:313–329. 2016.


Duperret EK, Liu S, Paik M, Trautz A, Stoltz R, Liu X, Ze K, Perales-Puchalt A, Reed C, Yan J, et al: A designer cross-reactive DNA immunotherapeutic vaccine that targets multiple MAGE-A family members simultaneously for cancer therapy. Clin Cancer Res. 24:6015–6027. 2018.


Smith HA, Cronk RJ, Lang JM and McNeel DG: Expression and immunotherapeutic targeting of the SSX family of cancer-testis antigens in prostate cancer. Cancer Res. 71:6785–6795. 2011.


Smith HA and McNeel DG: Vaccines targeting the cancer-testis antigen SSX-2 elicit HLA-A2 epitope-specific cytolytic T cells. J Immunother. 34:569–580. 2011.


Martínez-Puente DH, Pérez-Trujillo JJ, Zavala-Flores LM, García-García A, Villanueva-Olivo A, Rodríguez-Rocha H, Valdés J, Saucedo-Cárdenas O, Montes de Oca-Luna R and Loera-Arias MJ: Plasmid DNA for therapeutic applications in cancer. Pharmaceutics. 14:18612022.


Disis MLN, Guthrie KA, Liu Y, Coveler AL, Higgins DM, Childs JS, Dang Y and Salazar LG: Safety and outcomes of a plasmid DNA vaccine encoding the ERBB2 intracellular domain in patients with advanced-Stage ERBB2-positive breast cancer: A phase 1 nonrandomized clinical trial. JAMA Oncol. 9:71–78. 2023.


Huang X, Zhang G, Tang TY, Gao X and Liang TB: Personalized pancreatic cancer therapy: From the perspective of mRNA vaccine. Mil Med Res. 9:532022.


Rekoske BT, Smith HA, Olson BM, Maricque BB and McNeel DG: PD-1 or PD-L1 blockade restores antitumor efficacy following SSX2 epitope-modified DNA vaccine immunization. Cancer Immunol Res. 3:946–955. 2015.


Sobhani N, Scaggiante B, Morris R, Chai D, Catalano M, Tardiel-Cyril DR, Neeli P, Roviello G, Mondani G and Li Y: Therapeutic cancer vaccines: From biological mechanisms and engineering to ongoing clinical trials. Cancer Treat Rev. 109:1024292022.


Zhang R, Billingsley MM and Mitchell MJ: Biomaterials for vaccine-based cancer immunotherapy. J Control Release. 292:256–276. 2018.


Zhang C, Ma Y, Zhang J, Kuo JC, Zhang Z, Xie H, Zhu J and Liu T: Modification of lipid-based nanoparticles: An efficient delivery system for nucleic acid-based immunotherapy. Molecules. 27:19432022.


Papachristofilou A, Hipp MM, Klinkhardt U, Früh M, Sebastian M, Weiss C, Pless M, Cathomas R, Hilbe W, Pall G, et al: Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer. J Immunother Cancer. 7:382019.


Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, Maurus D, Schwarck-Kokarakis D, Kuhn AN, Omokoko T, et al: An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 585:107–112. 2020.


Van Hoecke L, Verbeke R, Dewitte H, Lentacker I, Vermaelen K, Breckpot K and Van Lint S: mRNA in cancer immunotherapy: Beyond a source of antigen. Mol Cancer. 20:482021.


Chen J, Chen J and Xu Q: Current developments and challenges of mRNA vaccines. Annu Rev Biomed Eng. 24:85–109. 2022.


He Q, Gao H, Tan D, Zhang H and Wang JZ: mRNA cancer vaccines: Advances, trends and challenges. Acta Pharm Sin B. 12:2969–2989. 2022.


Palmer CD, Rappaport AR, Davis MJ, Hart MG, Scallan CD, Hong SJ, Gitlin L, Kraemer LD, Kounlavouth S, Yang A, et al: Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: Phase 1 trial interim results. Nat Med. 28:1619–1629. 2022.


Lorentzen CL, Haanen JB, Met Ö and Svane IM: Clinical advances and ongoing trials on mRNA vaccines for cancer treatment. Lancet Oncol. 23:e450–e458. 2022.


Roy DG, Geoffroy K, Marguerie M, Khan ST, Martin NT, Kmiecik J, Bobbala D, Aitken AS, de Souza CT, Stephenson KB, et al: Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination. Nat Commun. 12:26262021.


Duan LJ, Wang Q, Zhang C, Yang DX and Zhang XY: Potentialities and challenges of mRNA vaccine in cancer immunotherapy. Front Immunol. 13:236472022.


Slingluff CL Jr, Petroni GR, Olson WC, Smolkin ME, Chianese-Bullock KA, Mauldin IS, Smith KT, Deacon DH, Varhegyi NE, Donnelly SB, et al: A randomized pilot trial testing the safety and immunologic effects of a MAGE-A3 protein plus AS15 immunostimulant administered into muscle or into dermal/subcutaneous sites. Cancer Immunol Immunother. 65:25–36. 2016.


Abd-Aziz N and Poh CL: Development of peptide-based vaccines for cancer. J Oncol. 2022:97493632022.


Bae J, Parayath N, Ma W, Amiji M, Munshi N and Anderson KC: BCMA peptide-engineered nanoparticles enhance induction and function of antigen-specific CD8+ cytotoxic T lymphocytes against multiple myeloma: Clinical applications. Leukemia. 34:19712020.


Kruit WH, Suciu S, Dreno B, Mortier L, Robert C, Chiarion-Sileni V, Maio M, Testori A, Dorval T, Grob JJ, et al: Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: Results of a randomized phase II study of the European organisation for research and treatment of cancer melanoma group in metastatic melanoma. J Clin Oncol. 31:2413–2420. 2013.


Goepfert PA, Tomaras GD, Horton H, Montefiori D, Ferrari G, Deers M, Voss G, Koutsoukos M, Pedneault L, Vandepapeliere P, et al: Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers. Vaccine. 25:510–518. 2007.


Du G and Sun X: Engineering nanoparticulate vaccines for enhancing antigen cross-presentation. Curr Opin Biotechnol. 66:113–122. 2020.


Warrier VU, Makandar AI, Garg M, Sethi G, Kant R, Pal JK, Yuba E and Gupta RK: Engineering anti-cancer nanovaccine based on antigen cross-presentation. Biosci Rep. 39:BSR201932202019.


Miyamoto A, Honjo T, Masui M, Kinoshita R, Kumon H, Kakimi K and Futami J: Engineering cancer/testis antigens with reversible S-cationization to evaluate antigen spreading. Front Oncol. 12:8693932022.


Zhang Y, Lin S, Wang XY and Zhu G: Nanovaccines for cancer immunotherapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 11:e15592019.


Wen R, Umeano AC, Kou Y, Xu J and Farooqi AA: Nanoparticle systems for cancer vaccine. Nanomedicine (Lond). 14:627–648. 2019.


Yang J, Li ZH, Zhou JJ, Chen RF, Cheng LZ, Zhou QB and Yang LQ: Preparation and antitumor effects of nanovaccines with MAGE-3 peptides in transplanted gastric cancer in mice. Chin J Cancer. 29:359–364. 2010.


Somaiah N, Block MS, Kim JW, Shapiro GI, Do KT, Hwu P, Eder JP, Jones RL, Lu H, Ter Meulen JH, et al: First-in-class, first-in-human study evaluating LV305, a dendritic-cell tropic lentiviral vector, in sarcoma and other solid tumors expressing NY-ESO-1. Clin Cancer Res. 25:5808–5817. 2019.


Deng Z, Tian Y, Song J, An G and Yang P: mRNA vaccines: The dawn of a new era of cancer immunotherapy. Front Immunol. 13:8871252022.


Chen W, Wu Y, Deng J, Yang Z, Chen J, Tan Q, Guo M and Jin Y: Phospholipid-membrane-based nanovesicles acting as vaccines for tumor immunotherapy: Classification, mechanisms and applications. Pharmaceutics. 14:24462022.


Wadman M: Public needs to prep for vaccine side effects. Science. 370:10222020.


Kudo K, Miki Y, Carreras J, Nakayama S, Nakamoto Y, Ito M, Nagashima E, Yamamoto K, Higuchi H, Morita SY, et al: Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma. Cell Metab. 34:615–633.e8. 2022.


Cheng Y, Jiao X, Fan W, Yang Z, Wen Y and Chen X: Controllable synthesis of versatile mesoporous organosilica nanoparticles as precision cancer theranostics. Biomaterials. 256:1201912020.


Li J, Lu W, Yang Y, Xiang R, Ling Y, Yu C and Zhou Y: Hybrid nanomaterials for cancer immunotherapy. Adv Sci (Weinh). 10:e22049322023.

Related Articles

Journal Cover

Volume 62 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
Spandidos Publications style
Ren S, Zhang Z, Li M, Wang D, Guo R, Fang X and Chen F: Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review). Int J Oncol 62: 71, 2023
Ren, S., Zhang, Z., Li, M., Wang, D., Guo, R., Fang, X., & Chen, F. (2023). Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review). International Journal of Oncology, 62, 71.
Ren, S., Zhang, Z., Li, M., Wang, D., Guo, R., Fang, X., Chen, F."Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review)". International Journal of Oncology 62.6 (2023): 71.
Ren, S., Zhang, Z., Li, M., Wang, D., Guo, R., Fang, X., Chen, F."Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review)". International Journal of Oncology 62, no. 6 (2023): 71.