期刊
MOLECULES
卷 26, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/molecules26020253
关键词
peptides; immune checkpoints; peptide microarray; cancer; immunotherapy
资金
- Russian Foundation for Basic Research [17-54-33003]
- Ministry of Science and Higher Education of the Russian Federation [FZMW-2020-0007]
- Tomsk Polytechnic University Competitiveness Enhancement Program
The discovery of immune checkpoints and their ligands has led to new possibilities for cancer immunotherapy. A synthetic peptide, p344, has been identified that specifically interacts with CTLA-4 protein, potentially blocking its interaction with B7-1 ligand. This peptide shows promise as a novel immune checkpoint inhibitor for cancer therapy.
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 (MYPPPY104)-M-99 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.
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