Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
June-2024 Volume 27 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2024 Volume 27 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma

  • Authors:
    • Minmin Hu
    • Hong Liu
    • Yubing Zhang
    • Dingyan Lu
    • Lin Zheng
    • Yonglin Wang
    • Shuaishuai Chen
    • Ting Liu
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China, Engineering Research Center for The Development and Application of Ethnic Medicine and TCM (Ministry of Education)/National Engineering Research Center of Miao's Medicines, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 254
    |
    Published online on: April 17, 2024
       https://doi.org/10.3892/etm.2024.12542
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Epidermal growth factor receptor variant III (EGFRvIII) is prominently expressed in various epithelial tumors. PD0721, a single‑chain antibody (scFv), has been developed to specifically target EGFRvIII. Although doxorubicin (DOX) is an essential treatment approach for glioblastoma (GBM), its toxic effects and limited targeting capabilities are a challenge. To overcome the above limitations, antibody‑drug conjugates (ADCs) have been developed to exploit the specificity of monoclonal antibodies in directing potent cytotoxic drugs to tumor cells expressing the target antigens. The present study aimed to conjugate DOX with PD0721 scFv to construct a PD0721‑DOX ADC targeting EGFRvIII and examine its targeting effect and in vitro anti‑GBM activity. PD0721‑DOX ADC was generated by combining PD0721 scFv with DOX, using dextran T‑10 as a linker. The drug‑to‑antibody ratio (DAR) was measured by ultraviolet and visible spectrophotometry (UV‑Vis). A series of techniques, including cytotoxicity assays, immunofluorescence, cell internalization and flow cytometry assays were employed to evaluate the targeting efficacy and anti‑GBM activity of the PD0721‑DOX ADC. Following the conjugation of PD0721 scFv with DOX, the UV‑Vis results showed a noticeable red shift in the maximum absorbance. The DAR of PD0721 scFv and DOX was 9.23:1. Cytotoxicity assays demonstrated that DK‑MG cells treatment with PD0721‑DOX ADC at 10 and 20 µg/ml significantly increased cytotoxicity compared with U‑87MG ATCC cells (all P<0.01). Confocal microscopy revealed distinct green and red fluorescence in EGFRvIII‑expressing DK‑MG cells, while no fluorescence was observed in EGFRvIII negative U‑87MG ATCC cells. Furthermore, compared with U‑87MG ATCC cells, DK‑MG cells showed effective internalization of the PD0721‑DOX ADC (P<0.001). Finally, flow cytometric analyses indicated that the PD0721‑DOX ADC significantly promoted the apoptosis of DK‑MG cells compared with U‑87MG ATCC cells (P<0.01). In summary, the current study suggested that the PD0721‑DOX ADC could exhibit a notable targeting efficacy and potent anti‑GBM activity.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS and Khasraw M: Management of glioblastoma: State of the art and future directions. CA Cancer J Clin. 70:299–312. 2020.PubMed/NCBI View Article : Google Scholar

2 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar

3 

Avazzadeh R, Vasheghani-Farahani E, Soleimani M, Amanpour S and Sadeghi M: Synthesis and application of magnetite dextran-spermine nanoparticles in breast cancer hyperthermia. Prog Biomater. 6:75–84. 2017.PubMed/NCBI View Article : Google Scholar

4 

Tang L, Jiang WH, Wu L, Yu XL, He Z, Shan WG, Fu LL, Zhang ZH and Zhao YC: TPGS2000-DOX prodrug micelles for improving breast cancer therapy. Int J Nanomedicine. 16:7875–7890. 2021.PubMed/NCBI View Article : Google Scholar

5 

Yang N, Ma HY, Jiang Z, Niu LH, Zhang XS, Liu YY, Wang YH, Cheng ST, Deng Y, Qi HY and Wang ZR: Dosing depending on SIRT3 activity attenuates doxorubicin-induced cardiotoxicity via elevated tolerance against mitochondrial dysfunction and oxidative stress. Biochem Biophys Res Commun. 517:111–117. 2019.PubMed/NCBI View Article : Google Scholar

6 

Aljobaily N, Viereckl MJ, Hydock DS, Aljobaily H, Wu TY, Busekrus R, Jones B, Alberson J and Han Y: Creatine alleviates doxorubicin-induced liver damage by inhibiting liver fibrosis, inflammation, oxidative stress and cellular senescence. Nutrients. 13(41)2020.PubMed/NCBI View Article : Google Scholar

7 

Guo Y, Ding YY, Zhang T and An HL: Sinapine reverses multi-drug resistance in MCF-7/dox cancer cells by downregulating FGFR4/FRS2α-ERK1/2 pathway-mediated NF-κB activation. Phytomedicine. 23:267–273. 2016.PubMed/NCBI View Article : Google Scholar

8 

Santos EDS, Nogueira KAB, Fernandes LCC, Martins JRP, Reis AVF, Neto JBV, Júnior I, Pessoa C, Petrilli R and Eloy JO: EGFR targeting for cancer therapy: Pharmacology and immunoconjugates with drugs and nanoparticles. Int J Pharm. 592(120082)2021.PubMed/NCBI View Article : Google Scholar

9 

Li MF, Yang JL, Zhang LH, Tu SF, Zhou X, Tan Z, Zhou WJ, He YJ and Li YH: A low-molecular-weight compound exerts anticancer activity against breast and lung cancers by disrupting EGFR/Eps8 complex formation. J Exp Clin Cancer Res. 38(211)2019.PubMed/NCBI View Article : Google Scholar

10 

Sigismund S, Avanzato D and Lanzetti L: Emerging functions of the EGFR in cancer. Mol Oncol. 12:3–20. 2018.PubMed/NCBI View Article : Google Scholar

11 

Hampton KK and Craven RJ: Pathways driving the endocytosis of mutant and wild-type EGFR in cancer. Oncoscience. 1:504–512. 2014.PubMed/NCBI View Article : Google Scholar

12 

Richards KN, Zweidler-McKay PA, Van Roy N, Speleman F, Trevino J, Zage PE and Hughes DP: Signaling of ERBB receptor tyrosine kinases promotes neuroblastoma growth in vitro and in vivo. Cancer. 116:3233–3243. 2010.PubMed/NCBI View Article : Google Scholar

13 

Gan HK, Cvrljevic AN and Johns TG: The epidermal growth factor receptor variant III (EGFRvIII): Where wild things are altered. FEBS J. 280:5350–5370. 2013.PubMed/NCBI View Article : Google Scholar

14 

Guo G, Gong K, Wohlfeld B, Hatanpaa KJ, Zhao D and Habib AA: Ligand-independent EGFR signaling. Cancer Res. 75:3436–3441. 2015.PubMed/NCBI View Article : Google Scholar

15 

Zheng Y, Ma Y, Yue H, Liu GZ and Han SY: EGFRvIII epigenetically regulates ARHI to promote glioma cell proliferation and migration. Exp Mol Pathol. 112(104344)2020.PubMed/NCBI View Article : Google Scholar

16 

Yang K, Ren X, Tao L, Wang P, Jiang H, Shen L, Zhao Y, Cui Y, Li M and Lin S: Prognostic implications of epidermal growth factor receptor variant III expression and nuclear translocation in Chinese human gliomas. Chin J Cancer Res. 31:188–202. 2019.PubMed/NCBI View Article : Google Scholar

17 

Zhang Z, Jiang J, Wu X, Zhang M, Luo D, Zhang R, Li S, He Y, Bian H and Chen Z: Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy. Front Med. 13:57–68. 2019.PubMed/NCBI View Article : Google Scholar

18 

Bagley SJ and O'Rourke DM: Clinical investigation of CAR T cells for solid tumors: Lessons learned and future directions. Pharmacol Ther. 205(107419)2020.PubMed/NCBI View Article : Google Scholar

19 

Wee P and Wang Z: Epidermal growth factor receptor cell proliferation signaling pathways. Cancers. 9(52)2017.PubMed/NCBI View Article : Google Scholar

20 

Nagayama A, Ellisen LW, Chabner B and Bardia A: Antibody-drug conjugates for the treatment of solid tumors: Clinical experience and latest developments. Target Oncol. 12:719–739. 2017.PubMed/NCBI View Article : Google Scholar

21 

Sievers EL and Senter PD: Antibody-drug conjugates in cancer therapy. Annu Rev Med. 64:15–29. 2013.PubMed/NCBI View Article : Google Scholar

22 

Okajima D, Yasuda S, Maejima T, Karibe T, Sakurai K, Aida T, Toki T, Yamaguchi J, Kitamura M, Kamei R, et al: Datopotamab deruxtecan, a novel TROP2-directed antibody-drug conjugate, demonstrates potent antitumor activity by efficient drug delivery to tumor cells. Mol Cancer Ther. 20:2329–2340. 2021.PubMed/NCBI View Article : Google Scholar

23 

Hafeez U, Parakh S, Gan HK and Scott AM: Antibody-drug conjugates for cancer therapy. Molecules. 25(4764)2020.PubMed/NCBI View Article : Google Scholar

24 

Zhang YB, Wu ZX, He B, Yang C, Li YJ and Liu T: Establishment and optimization of an ELISA for affinity detection of single-chain antibodies to EGFRvIII. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 37:73–78. 2021.PubMed/NCBI(In Chinese).

25 

Zhang YB, Ye LF, Wu ZX, Xue WN, He B, Yang C, Li YJ, Wang YL and Liu T: Optimization and identification of prokaryotic expression conditions of PD0721 single-chain antibody in vitro. J Food Sci Biotech. 40:42–49. 2021.

26 

Struve N, Riedel M, Schulte A, Rieckmann T, Grob TJ, Gal A, Rothkamm K, Lamszus K, Petersen C, Dikomey E and Kriegs M: EGFRvIII does not affect radiosensitivity with or without gefitinib treatment in glioblastoma cells. Oncotarget. 6:33867–33877. 2015.PubMed/NCBI View Article : Google Scholar

27 

Allen M, Bjerke M, Edlund H, Nelander S and Westermark B: Origin of the U87MG glioma cell line: Good news and bad news. Sci Transl Med. 8(354re3)2016.PubMed/NCBI View Article : Google Scholar

28 

Zraik IM and Heß-Busch Y: Management of chemotherapy side effects and their long-term sequelae. Urologe A. 60:862–871. 2021.PubMed/NCBI View Article : Google Scholar : (In German).

29 

Fu ZW, Li SJ, Han SF, Shi C and Zhang Y: Antibody drug conjugate: The ‘biological missile’ for targeted cancer therapy. Signal Transduct Target Ther. 7(93)2022.PubMed/NCBI View Article : Google Scholar

30 

Hu QB, Lu YJ and Luo YC: Recent advances in dextran-based drug delivery systems: From fabrication strategies to applications. Carbohydr Polym. 264(117999)2021.PubMed/NCBI View Article : Google Scholar

31 

Helal MH, Al-Mudaris ZA, Al-Douh MH, Osman H, Wahab HA, Alnajjar BO, Abdallah HH and Abdul Majid AM: Diaminobenzene schiff base, a novel class of DNA minor groove binder. Int J Oncol. 41:504–510. 2012.PubMed/NCBI View Article : Google Scholar

32 

Marei HE, Cenciarelli C and Hasan A: Potential of antibody-drug conjugates (ADCs) for cancer therapy. Cancer Cell Int. 22(255)2022.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Hu M, Liu H, Zhang Y, Lu D, Zheng L, Wang Y, Chen S and Liu T: Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma. Exp Ther Med 27: 254, 2024.
APA
Hu, M., Liu, H., Zhang, Y., Lu, D., Zheng, L., Wang, Y. ... Liu, T. (2024). Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma. Experimental and Therapeutic Medicine, 27, 254. https://doi.org/10.3892/etm.2024.12542
MLA
Hu, M., Liu, H., Zhang, Y., Lu, D., Zheng, L., Wang, Y., Chen, S., Liu, T."Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma". Experimental and Therapeutic Medicine 27.6 (2024): 254.
Chicago
Hu, M., Liu, H., Zhang, Y., Lu, D., Zheng, L., Wang, Y., Chen, S., Liu, T."Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma". Experimental and Therapeutic Medicine 27, no. 6 (2024): 254. https://doi.org/10.3892/etm.2024.12542
Copy and paste a formatted citation
x
Spandidos Publications style
Hu M, Liu H, Zhang Y, Lu D, Zheng L, Wang Y, Chen S and Liu T: Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma. Exp Ther Med 27: 254, 2024.
APA
Hu, M., Liu, H., Zhang, Y., Lu, D., Zheng, L., Wang, Y. ... Liu, T. (2024). Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma. Experimental and Therapeutic Medicine, 27, 254. https://doi.org/10.3892/etm.2024.12542
MLA
Hu, M., Liu, H., Zhang, Y., Lu, D., Zheng, L., Wang, Y., Chen, S., Liu, T."Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma". Experimental and Therapeutic Medicine 27.6 (2024): 254.
Chicago
Hu, M., Liu, H., Zhang, Y., Lu, D., Zheng, L., Wang, Y., Chen, S., Liu, T."Preparation and evaluation of the PD0721‑DOX antibody‑drug conjugate targeting EGFRvIII to inhibit glioblastoma". Experimental and Therapeutic Medicine 27, no. 6 (2024): 254. https://doi.org/10.3892/etm.2024.12542
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team