Immune responses of patients without cancer recurrence after a cancer vaccine over a long term

Suekane,Shigetaka; Yutani,Shigeru; Toh,Uhi; Yoshiyama,Koichi; Itoh,Kyogo

doi:10.3892/mco.2022.2545

Immune responses of patients without cancer recurrence after a cancer vaccine over a long term

Authors:
- Shigetaka Suekane
- Shigeru Yutani
- Uhi Toh
- Koichi Yoshiyama
- Kyogo Itoh
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Affiliations: Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Kurume Cancer Vaccine Center, Kurume University, Kurume, Fukuoka 830‑0011, Japan, Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
Published online on: May 13, 2022 https://doi.org/10.3892/mco.2022.2545
Article Number: 112
Copyright: © Suekane et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to clarify the humoral and cellular immune responses of patients with cancer who experienced no recurrence over a long term after receiving a cancer vaccine. The immune kinetics were investigated in response to a personalized peptide vaccination (PPV) among 44 Japanese patients without an active tumor at entry to the vaccination: Lung adenocarcinoma (n=11); colon (n=18); and breast cancer (n=15) (9, 10, 12, 8 and 5 patients with stage I, II, III and IV recurrences, respectively). The patients' immunoglobulin G (IgG) and cytotoxic T lymphocyte (CTL) activities were measured using a multiplexed Luminex assay and an interferon‑γ release assay, respectively. There were no severe adverse events related to the PPV other than a grade III injection site reaction. A potent boost in IgG or CTL at the end of the 1st vaccination cycle was observed in 77% of the patients (n=84). The IgG levels were sustained throughout the follow‑up period, whereas the CTL levels declined and were transient. A total of 37 of the 44 patients (84%) had no recurrence, with a median follow‑up of 67.6 months (interquartile range, 45.6‑82.8 months). Overall, the PPV induced long‑term humoral immunity with transient cellular immunity in the majority of patients with cancer without an active tumor at their entry to the PPV.

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1	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.PubMed/NCBI View Article : Google Scholar
2	Xiang B, Snook AE, Magee MS and Waldman SA: Colorectal cancer immunotherapy. Discov Med. 15:301–308. 2013.PubMed/NCBI
3	Mittendorf EA, Lu B, Melisko M, Price Hiller J, Bondarenko I, Brunt AM, Sergii G, Petrakova K and Peoples GE: Efficacy and safety analysis of Nelipepimut-S vaccine to prevent breast cancer recurrence: A randomized, multicenter, phase III clinical trial. Clin Cancer Res. 25:4248–4254. 2019.PubMed/NCBI View Article : Google Scholar
4	Clifton GT, Hale D, Vreeland TJ, Hickerson AT, Litton JK, Alatrash G, Murthy RK, Qiao N, Philips AV, Lukas JJ, et al: Results of a randomized phase IIb trial of Nelipepimut-S + Trastuzumab versus Trastuzumab to prevent recurrences in patients with high-risk HER2 low-expressing breast cancer. Clin Cancer Res. 26:2515–2523. 2020.PubMed/NCBI View Article : Google Scholar
5	Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 366:2443–2454. 2012.PubMed/NCBI View Article : Google Scholar
6	Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 366:2455–2465. 2012.PubMed/NCBI View Article : Google Scholar
7	Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins CM, Jenkins D, Schuind A, Costa Clemens SA and Dubin G: HPV Vaccine Study group. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: Follow-up from a randomised control trial. Lancet. 367:1247–1255. 2006.PubMed/NCBI View Article : Google Scholar
8	Rosenbaum P, Artaud C, Bay S, Ganneau C, Campone M, Delaloge S, Gourmelon C, Loirat D, Medioni J, Pein F, et al: The fully synthetic glycopeptide MAG-Tn3 therapeutic vaccine induces tumor-specific cytotoxic antibodies in breast cancer patients. Cancer Immunol Immunother. 69:703–716. 2020.PubMed/NCBI View Article : Google Scholar
9	Gupta S, McDonald JD, Ayabe RI, Khan TM, Gamble LA, Sinha S, Hannah C, Blakely AM, Davis JL and Hernandez JM: Targeting CA 19-9 with a humanized monoclonal antibody at the time of surgery may decrease recurrence rates for patients undergoing resections for pancreatic cancer, cholangiocarcinoma and metastatic colorectal cancer. J Gastrointest Oncol. 11:231–235. 2020.PubMed/NCBI View Article : Google Scholar
10	van der Meijden PM, van Klingeren B, Steerenberg PA, de Boer LC, de Jong WH and Debruyne FM: The possible influence of antibiotics on results of bacillus Calmette-Guérin intravesical therapy for superficial bladder cancer. J Urol. 146:444–446. 1991.PubMed/NCBI View Article : Google Scholar
11	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.PubMed/NCBI View Article : Google Scholar
12	Bezu L, Kepp O, Cerrato G, Pol J, Fucikova J, Spisek R, Zitvogel L, Kroemer G and Galluzzi L: Trial watch: Peptide-based vaccines in anticancer therapy. Oncoimmunology. 7(e1511506)2018.PubMed/NCBI View Article : Google Scholar
13	Sasada T, Yamada A, Noguchi M and Itoh K: Personalized peptide vaccine for treatment of advanced cancer. Curr Med Chem. 21:2332–2345. 2014.PubMed/NCBI View Article : Google Scholar
14	Noguchi M, Sasada T and Itoh K: Personalized peptide vaccination: A new approach for advanced cancer as therapeutic cancer vaccine. Cancer Immunol Immunother. 62:919–929. 2013.PubMed/NCBI View Article : Google Scholar
15	Narita Y, Arakawa Y, Yamasaki F, Nishikawa R, Aoki T, Kanamori M, Nagane M, Kumabe T, Hirose Y, Ichikawa T, et al: A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma. Neuro Oncol. 21:348–359. 2019.PubMed/NCBI View Article : Google Scholar
16	Noguchi M, Fujimoto K, Arai G, Uemura H, Hashine K, Matsumoto H, Fukasawa S, Kohjimoto Y, Nakatsu H, Takenaka A, et al: A randomized phase III trial of personalized peptide vaccination for castration-resistant prostate cancer progressing after docetaxel. Oncol Rep. 45:159–168. 2021.PubMed/NCBI View Article : Google Scholar
17	Suekane S, Yutani S, Yamada A, Sasada T, Matsueda S, Takamori S, Toh U, Kawano K, Yoshiyama K, Sakamoto S, et al: Identification of biomarkers for personalized peptide vaccination in 2,588 cancer patients. Int J Oncol. 56:1479–1489. 2020.PubMed/NCBI View Article : Google Scholar
18	Matsueda S, Itoh K and Shichijo S: Antitumor activity of antibody against cytotoxic T lymphocyte epitope peptide of lymphocyte-specific protein tyrosine kinase. Cancer Sci. 109:611–617. 2018.PubMed/NCBI View Article : Google Scholar
19	Noguchi M, Koga N, Moriya F, Suekane S, Yutani S, Yamada A, Shichijo S, Kakuma T and Itoh K: Survival analysis of multiple peptide vaccination for the selection of correlated peptides in urological cancers. Cancer Sci. 109:2660–2669. 2018.PubMed/NCBI View Article : Google Scholar
20	Taskén K: Waking up regulatory T cells. Blood. 114:1136–1137. 2009.PubMed/NCBI View Article : Google Scholar
21	Bardhan K, Patsoukis N, Weaver J, Freeman G, Li L and Boussiotis VA: PD-1 inhibits the TCR signaling cascade by sequestering SHP-2 phosphatase, preventing its translocation to lipid rafts and facilitating Csk-mediated inhibitory phosphorylation of Lck. J Immunol 196 (Suppl 1). 128(15)2016.
22	Dunn GP, Old LJ and Schreiber RD: The three Es of cancer immunoediting. Annu Rev Immunol. 22:329–360. 2004.PubMed/NCBI View Article : Google Scholar
23	Thomas R, Al-Khadairi G, Roelands J, Hendrickx W, Dermime S, Bedognetti D and Decock J: NY-ESO-1 based immunotherapy of cancer: Current perspectives. Front Immunol. 9(947)2018.PubMed/NCBI View Article : Google Scholar
24	Zitvogel L, Ayyoub M, Routy B and Kroemer G: Microbiome and anticancer immunosurveillance. Cell. 165:276–287. 2016.PubMed/NCBI View Article : Google Scholar
25	Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, et al: Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 350:1084–1089. 2015.PubMed/NCBI View Article : Google Scholar