The Protective and Therapeutic Effect of DNA Vaccine Derived From Immunogenic Components of BORIS Antigen on Colon Cancer in Balb/C Mice

Document Type : Original Article (s)

Authors

1 Department of Biology, School of Science and Engineering, Science and Arts University, Yazd, Iran

2 Assistant Professor, Department Radiotherapy, School of Paramedicine, Arak University of Medical Sciences, Arak, Iran

3 Assistant Professor, Department of Biology, School of Science and Engineering, Science and Arts University, Yazd, Iran

4 Professor, Skin Diseases and Leishmaniasis Research Center AND Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Immunotherapy is a new strategy to prevent and treat cancers. Cancer-testis antigens has gained lots of attention as the target of anti-cancer immunotherapy. In this study, Brother of regulator of imprinted sites (BORIS) cancer-testis antigen was used to design a DNA vaccine using bioinformatics tools, and its efficacy was assessed in murine colon cancer model in Balb/C mice.Methods: In our previous study, the immunodominant regions of the BORIS antigen were identified. They were used to design a DNA vaccine inside the pcDNA3.1 plasmid after appropriate modifications and reverse translation. The DNA vaccine was used to immunized BALB/c mice four times at weekly intervals. 14 days after the last injection, the levels of specific cytokines and antibodies were measured. Moreover, to evaluate the protective effect of the DNA vaccine, colorectal cancer cells (CT26) were injected into mice, and tumors’ growth progression evaluated for 28 days.Findings: Vaccination with this multiepitope DNA vaccine increased the level of gamma interferon (IFN-γ) and interleukin 4 (IL-4) cytokines (P < 0.001) and specific antibodies [immunoglobulin G1 (IgG1), IgG2a, IgG total] (P < 0.001) compared to control groups [phosphate buffered saline (PBS) and pcDNA3.1-VAC]. Moreover, mean tumors volume significantly decreased (P < 0.001) in the DNA vaccine immunized group compared to control groups.Conclusion: This study suggests that the use of a BORIS antigen-derived DNA vaccine can be used as a strategy to induce a significant anti-tumor immune response, and inhibit murine colon tumors growth.

Keywords

References

  1. Stein A, Folprecht G. Immunotherapy of colon cancer. Oncol Res Treat 2018; 41(5): 282-5.
  2. Jahanafrooz Z, Baradaran B, Mosafer J, Hashemzaei M, Rezaei T, Mokhtarzadeh A, et al. Comparison of DNA and mRNA vaccines against cancer. Drug Discov Today 2020; 25(3): 552-60.
  3. Padda IS, Parmar M. COVID (SARS-COV-2) Vaccine. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021
  4. Porter KR, Raviprakash K. DNA vaccine delivery and improved immunogenicity. Curr Issues Mol Biol 2017; 22: 129-38.
  5. Gary EN, Weiner DB. DNA vaccines: Prime time is now. Curr Opin Immunol 2020; 65: 21-7.
  6. Jameson SC, Masopust D. Understanding subset diversity in T cell memory. Immunity 2018; 48(2): 214-26.
  7. Whitehurst AW. Cause and consequence of cancer/testis antigen activation in cancer. Annu Rev Pharmacol Toxicol 2014; 54: 251-72.
  8. Bode PK, Thielken A, Brandt S, Barghorn A, Lohe B, Knuth A, et al. Cancer testis antigen expression in testicular germ cell tumorigenesis. Mod Pathol 2014; 27(6): 899-905.
  9. Fan C, Qu H, Wang X, Sobhani N, Wang L, Liu S, et al. Cancer/testis antigens: from serology to mRNA cancer vaccine. Semin Cancer Biol 2021. [Epub ahead of print].
  10. Al-Khadairi G, Decock J. Cancer testis antigens and immunotherapy: Where do we stand in the targeting of PRAME? Cancers (Basel) 2019; 11(7).
  11. Zajac P, Schultz-Thater E, Tornillo L, Sadowski C, Trella E, Mengus C, et al. MAGE-A Antigens and cancer immunotherapy. Front Med (Lausanne) 2017; 4: 18.
  12. Fratta E, Coral S, Covre A, Parisi G, Colizzi F, Danielli R, et al. The biology of cancer testis antigens: Putative function, regulation and therapeutic potential. Mol Oncol 2011; 5(2): 164-82.
  13. Ogunkolade BW, Jones TA, Aarum J, Szary J, Owen N, Ottaviani D, et al. BORIS/CTCFL is an RNA-binding protein that associates with polysomes. BMC Cell Biol 2013; 14: 52.
  14. Martin-Kleiner I. BORIS in human cancers -- a review. Eur J Cancer 2012; 48(6): 929-35.
  15. Tiffen JC, Bailey CG, Marshall AD, Metierre C, Feng Y, Wang Q, et al. The cancer-testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells. Int J Cancer 2013; 133(7): 1603-13.
  16. Mahdevar E, Safavi A, Abiri A, Kefayat A, Hejazi SH, Miresmaeili SM, et al. Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches. J Biomol Struct Dyn 2021; 1-18.
  17. Mkrtichyan M, Ghochikyan A, Davtyan H, Movsesyan N, Loukinov D, Lobanenkov V, et al. Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma. Cell Immunol 2011; 270(2): 188-97.
  18. Loukinov D, Ghochikyan A, Mkrtichyan M, Ichim TE, Lobanenkov VV, Cribbs DH, et al. Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. J Cell Biochem 2006; 98(5): 1037-43.
  19. Ghochikyan A, Mkrtichyan M, Loukinov D, Mamikonyan G, Pack SD, Movsesyan N, et al. Elicitation of T cell responses to histologically unrelated tumors by immunization with the novel cancer-testis antigen, brother of the regulator of imprinted sites. J Immunol 2007; 178(1): 566-73.
  20. Loukinov D. Targeting CTCFL/BORIS for the immunotherapy of cancer. Cancer Immunol Immunother 2018; 67(12): 1955-65.

Files

History

  • Receive Date: 02 May 2021
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics