Skip to main content
SpringerLink
Log in

Development of Search Strategy for Peptide Inhibitors of Immune Checkpoints

  • Published:
Russian Journal of Bioorganic Chemistry Aims and scope Submit manuscript

Abstract

Current strategy for the blockade of molecules inhibiting T-cell immunity, the immune checkpoints (ICP), such as CTLA-4, PD-1, and B7-H1(PD-L1), using monoclonal antibodies (mAbs), showed significant clinical effects in cancer immunotherapy. In this kind of therapy, antibodies do not kill tumor cells directly, but block inhibitory signals for T lymphocytes, resulting in activation of the immune response cascade that eliminate malignant cells and lead to tumor degradation. However, the mAb preparations have some limitations, and the development of new low-molecular-weight antagonists (for example, peptides) is an important issue. In this study, we used peptide microarrays and phage display libraries to search for peptides that interact with the immune checkpoints. We found peptides that specifically bind CTLA-4, PD-1, B7-1, B7-2 and B7-H1(PD-L1) which play important role in the regulation of the immune responses. These synthetic peptides can be applied to the development of new immunomodulating drugs for cancer immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CTLA-4:

the cytotoxic receptor 4 of a T-lymphocyte

PD-1:

the receptor of the programmed cell death for a T-lymphocyte

В7-1/2 and B7-H1(PD-L1):

ligands of the CTLA-4 and PD-1 receptors

ICP:

immune checkpoint

mAb:

monoclonal antibody

TCR:

T-cellular receptor

MHC:

major histocompatibility complex

References

  1. Abelev, G.I., Soros. Obrazovat. Zh., 1996, no. 5, pp. 4–10.

    Google Scholar 

  2. Grosso, F.J. and Jure-Kunkel, M.N., Cancer Immun., 2013, vol. 13, pp. 5–14.

    PubMed  PubMed Central  Google Scholar 

  3. Buchbinder, E.I. and Desai, A., Am. J. Clin. Oncol., 2016, vol. 39, pp. 98–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Postow, M.A., Callahan, M.K., and Wolchok, J.D., J. Clin. Oncol., 2015, vol. 33, pp. 1974–1982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pardoll, D.M., Nat. Rev. Cancer, 2012, vol. 12, pp. 252–264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sharma, P. and Allison, J.P., Science, 2015, vol. 348, pp. 56–61.

    Article  CAS  PubMed  Google Scholar 

  7. Freidlin, I.S., Med. Immunol., 2005, vol. 7, no. 4, pp. 347–354.

    Article  Google Scholar 

  8. Athanassakis, I. and Vassiliadis, S., Immunol. Lett., 2002, vol. 84, pp. 179–183.

    Article  CAS  PubMed  Google Scholar 

  9. Saito, T. and Yamasaki, S., Immunol. Rev., 2003, vol. 192, pp. 143–160.

    Article  CAS  PubMed  Google Scholar 

  10. Medina, P.J. and Adams, V.R., Pharmacotherapy, 2016, vol. 36, pp. 317–334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Haspot, F., Fehr, T., Gibbons, C., Zhao, G., Hogan, T., Honjo, T., Freeman, G.J., and Sykes, M., Blood, 2008, vol. 112, pp. 2149–2155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kadagidze, Z.G., Chertkova, A.I., Zabotina, T.N., Korotkova, O.V., Slavina, E.G., and Borunova, A.A., Zh. Zlokachestv. Opukh., 2015, no. 1, pp. 24–31.

    Google Scholar 

  13. Walunas, T.L., Lenschow, D.J., Bakker, C.Y., Linsley, P.S., Freeman, G.J., Green, J.M., Thompson, C.B., and Bluestone, J.A., Immunity, 1994, vol. 1, pp. 405–413.

    Article  CAS  PubMed  Google Scholar 

  14. Brahmer, J.R., Clin. Adv. Hematol. Oncol., 2012, vol. 10, pp. 674–675.

    PubMed  Google Scholar 

  15. Shapoval, A.I., Podlesnykh, S.V., Kolosova, E.A., and Shcherbakov, D.N., Ross. Onkol. Zh., 2017, no. 4, pp. 175–179.

    Google Scholar 

  16. Vlieghe, P., Lisowski, V., Martinez, J., and Khrestchatisky, M., Drug Discov. Today, 2010, vol. 15, pp. 40–56.

    Article  CAS  PubMed  Google Scholar 

  17. Skerra, A., Curr. Opin. Biotechnol., 2007, vol. 18, pp. 295–304.

    Article  CAS  PubMed  Google Scholar 

  18. Volpe, M., J. Cardiol., 2014, vol. 176, pp. 630–639.

    Google Scholar 

  19. Fosgerau, K. and Hoffmann, T., Drug Discov. Today, 2015, vol. 20, pp. 122–128.

    Article  CAS  PubMed  Google Scholar 

  20. Brandt, C.R., J. Ocul. Pharmacol. Ther., 2014, vol. 30, pp. 691–699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schluter, N., De Sterke, A., Willmes, D.M., Spranger, J., Jordan, J., and Birkenfeld, A.L., Pharmacol. Ther., 2014, vol. 144, pp. 12–27.

    Article  Google Scholar 

  22. Podlesnykh, S.V., Kolosova, E.A., Shcherbakov, D.N., Shaidurov, A.A., Anisimov, D.S., Ryazanov, M.A., Johnston, S.A., Shoikhet, Y.N., Petrova, V.D., Lazarev, A.F., and Chapoval, A.I., Bull. Exp. Biol. Med., 2016, vol. 161, pp. 816–820.

    Article  CAS  PubMed  Google Scholar 

  23. Shengdian, W., Gefeng, Z., Koji, T., Lieping, C., and Jürgen, B., J. Exp. Med., 2002, vol. 195, pp. 1033–1041.

    Article  Google Scholar 

  24. Lee, J.Y., Lee, H.T., Shin, W., Chae, J., Choi, J., Kim, S.H., Lim, H., Heo, T.W., Park, K.Y., Lee, Y.J., Ryu, S.E., Son, J.Y., Lee, J.U., and Heo, Y.S., Nat. Commun., 2016, vol. 7, p. 13354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Legutki, J.B., Zhao, Z.G., Greving, M., Woodbury, N., Johnston, S.A., and Stafford, P., Nature Commun., 2014, vol. 5, p. 4785.

    Article  CAS  Google Scholar 

  26. Shcherbakova, N.S., Chikaev, A.N., Karpenko, L.I., and Il’ichev, A.A., Mol. Gen. Microb. Virol., 2012, vol. 27, pp. 22–27.

    Article  Google Scholar 

  27. Tolmacheva, V.V., Apyari, V.V., Ibragimova, B.N., Kochuk, E.V., Dmitrienko, S.G., and Zolotov, Yu.A., Zh. Anal. Khim., 2015, vol. 70, pp. 1149–1158.

    Google Scholar 

  28. Ph.D.™Phage Display Libraries. Instructional Manual, New England BioLabs Inc.

Download references

Author information

Author notes

  1. These authors equally contributed to the study. S.V. Podlesnykh was a winner of the Contest of Young Scientists.

Authors and Affiliations

  1. Russian-American Anti-Cancer Center, Altai State University, Barnaul, Altaiskii krai, 656049, Russia

    S. V. Podlesnykh, E. A. Kolosova, D. N. Shcherbakov & A. I. Chapoval

  2. ”VECTOR” State Research Center of Virology and Biotechnology, Koltsovo, 630559, Russia

    D. V. Shanshin, D. E. Murashkin, O. N. Shaprova & D. N. Shcherbakov

  3. Center for Innovations in Medicine, Biodesign Institute, Arizona State University, Tempe, AZ, 85287, United States

    A. I. Chapoval

Authors
  1. S. V. Podlesnykh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. V. Shanshin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Kolosova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. E. Murashkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. O. N. Shaprova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. N. Shcherbakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. I. Chapoval
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. V. Podlesnykh.

Additional information

This article is published based on the report on the Contest of Young Scientists that was held during the VIII Russian Symposium Proteins and Peptides at the Institute of Bioorganic Chemistry in Moscow, September 18–22, 2017.

Original Russian Text © S.V. Podlesnykh, D.V. Shanshin, E.A. Kolosova, D.E. Murashkin, O.N. Shaprova, D.N. Shcherbakov, A.I. Chapoval, 2018, published in Bioorganicheskaya Khimiya, 2018, Vol. 44, No. 2, pp. 138–145.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Podlesnykh, S.V., Shanshin, D.V., Kolosova, E.A. et al. Development of Search Strategy for Peptide Inhibitors of Immune Checkpoints. Russ J Bioorg Chem 44, 150–157 (2018). https://doi.org/10.1134/S1068162018020024

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162018020024

Keywords

Search

Navigation