MULTITARGET ANTI-PD-1/PD-L1/CD19/CD25/CD38 THERAPY USING CHELATE NANOCOMPLEX MSC-428 IN ONCOPATHOLOGY

Abstract

Over the past decade, there has been a deepening of ideas about the relationship between the tumor and the host’s immune system, as evidenced by the 2018 Nobel Prize in medicine and physiology for studying the role of the so-called. Immune checkpoints in neoplasm care from an attack of the host’s immune system. This mechanism is associated with the appearance on the surface of tumor cells of specific proteins – PD-1/PD-L-1, which prevent contact with the killer lymphocyte receptor. Chelate nanocomplexes (MSC-428) target PD-1/PD-L-1, i. e. affect the immune checkpoints directly. MSC-428 molecules attack 4 target proteins: PD-1/PD-L1, CD19, CD25, CD38, which leads to the normalization of surface antigens – CD3, CD4, CD8, CD16, CD45, CD95 lymphocytes, phagocytosis systems and immunoglobulins of class A, M, G. The proposed strategy of treatment against PD-1/PD-L-1 with the use of metal-containing nanocomplex MSC428 expands the possibilities of influencing immune checkpoints. Through conformational change in the 3-dimensional structure of the receptor proteins PD-1, the drug prevents them from binding to PD-L1 in tumor cells. This increases the expression of CD25 on T-lymphocytes, normalizes the production of IL-2, which increases the activity of T-killers against tumor cells. The drug reduces the activity of CD19 molecules, which shield tumor antigens and prevent the attack of cytotoxic T cells. As a result of inhibition of ZAP-70 kinase, CD38 expression is reduced, which increases the body’s antitumor response and mobilizes the cytotoxic potential of CD8 and CD16 T lymphocytes, preventing the development of tumor cell resistance. The restoration of their activity largely predetermines the normalization of other lymphocyte subpopulations, in particular, expressing CD3, CD4, CD8, CD16, CD95, as well as the restoration of the phagocytosis system, production of immunoglobulins of class A, M, G. Such a complex effect ensures the construction of a coherent and effective strategy for immunotherapy of patients with oncopathology.

Keywords

• multitarget therapy
• nanocomplexes
• oncopathology