Russian Journal of Bioorganic Chemistry

, Volume 44, Issue 2, pp 150–157 | Cite as

Development of Search Strategy for Peptide Inhibitors of Immune Checkpoints

  • S. V. Podlesnykh
  • D. V. Shanshin
  • E. A. Kolosova
  • D. E. Murashkin
  • O. N. Shaprova
  • D. N. Shcherbakov
  • A. I. Chapoval
Article
  • 6 Downloads

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.

Keywords

synthetic peptides co-stimulatory molecules immune checkpoints immune response peptide microchips immunotherapy immunomodulation phage display 

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

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • S. V. Podlesnykh
    • 1
  • D. V. Shanshin
    • 2
  • E. A. Kolosova
    • 1
  • D. E. Murashkin
    • 2
  • O. N. Shaprova
    • 2
  • D. N. Shcherbakov
    • 1
    • 2
  • A. I. Chapoval
    • 1
    • 3
  1. 1.Russian-American Anti-Cancer CenterAltai State UniversityBarnaul, Altaiskii kraiRussia
  2. 2.”VECTOR” State Research Center of Virology and BiotechnologyKoltsovoRussia
  3. 3.Center for Innovations in Medicine, Biodesign InstituteArizona State UniversityTempeUnited States

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