Peptide Blocking CTLA-4 and B7-1 Interaction

Molecules

AndreiI. Khlebnikov¹  AndreiI. Chapoval²  Anastasia Gordeeva²  StepanV. Podlesnykh²  KristinaE. Abramova² 

[1] Kizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin St., 634050 Tomsk, Russia;Russian-American Anti-Cancer Center, Altai State University, 61 Lenin St., 656049 Barnaul, Russia;

关键词: peptides;    immune checkpoints;    peptide microarray;    cancer;    immunotherapy;   

DOI  :  10.3390/molecules26020253

来源: DOAJ

【 摘 要 】

Discovery of the B7 family immune checkpoints such as CTLA-4 (CD152), PD-1 (CD279), as well as their ligands B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), and B7-DC (PD-L2, CD273), has opened new possibilities for cancer immunotherapy using monoclonal antibodies (mAb). The blockade of inhibitory receptors (CTLA-4 and PD-1) with specific mAb results in the activation of cancer patients’ T lymphocytes and tumor rejection. However, the use of mAb in clinics has several limitations including side effects and cost of treatment. The development of new low-molecular compounds that block immune checkpoints’ functional activity can help to overcome some of these limitations. In this paper, we describe a synthetic peptide (p344) containing 14 amino acids that specifically interact with CTLA-4 protein. A 3D computer model suggests that this peptide binds to the ⁹⁹MYPPPY¹⁰⁴ loop of CTLA-4 protein and potentially blocks the contact of CTLA-4 receptor with B7-1 ligand. Experimental data confirm the peptide-specific interaction with CTLA-4 and its ability to partially block CTLA-4/B7-1 binding. The identified synthetic peptide can be used for the development of novel immune checkpoint inhibitors that can block CTLA-4 functional activity for cancer immunotherapy.

【 授权许可】

Unknown