ABSTRACT
Current advances in research of immune checkpoints CTLA-4, PD-1, PD-L1, opened new possibilities for effective cancer immunotherapy using monoclonal antibodies. However, antibodies have a number of limitations for clinical use, which provides a basis for the search for low molecular weight compounds capable of regulating (blocking) molecules that inhibit the immune response. This paper presents the results of molecular docking and evaluation of synthetic peptide interaction with a CTLA-4 molecule. Using mathematical modeling, it was shown that peptides interacted with the 99MYPPPY104 loop of the CTLA-4 protein and could potentially block the interaction of the CTLA-4 receptor with its natural ligand B7-1. The specificity of the interaction between the identified peptide and recombinant chimeric CTLA-4 protein was evaluated. The detected synthetic peptide can be used for the development of immunomodulatory drugs for therapy of cancer or autoimmune diseases.
Subject(s)
Antineoplastic Agents, Immunological/chemistry , CTLA-4 Antigen/antagonists & inhibitors , Peptides/chemistry , Humans , Immunotherapy , Molecular Docking SimulationABSTRACT
The blood serum of tumor patients contains antibodies recognizing tumor-associated antigens and other molecular products of tumor growth. We studied the interaction of blood antibodies from breast cancer patients with synthetic peptides that were applied on the microchip surface. The serum from healthy volunteers and breast cancer patients was shown to contain antibodies that interact with various peptides. Statistically significant between-group differences were observed in the level of binding with 122 informative peptides (0.01% of the total number of peptides on a microchip). Analysis of antibodies that interact with the peptide panel holds much promise for the diagnostics of breast cancer.
