Construction of the systemic anticancer immune environment in tumour-bearing humanized mouse by using liposome-encapsulated anti-programmed death ligand 1 antibody-conjugated progesterone

نویسندگان

چکیده

Immune checkpoint inhibitors highlight the importance of anticancer immunity. However, their clinical utility and safety are limited by low response rates adverse effects. We focused on progesterone (P4), a hormone produced placenta during pregnancy, because it has multiple biological activities related to immune regulation P4 reversible regulatory function distinct from that stress cortisol, which may drive irreversible suppression promotes T cell exhaustion apoptosis in patients with cancer. Because effect is induced at higher than physiological concentrations, we aimed develop new drug encapsulating liposomes. In this study, prepared liposome-encapsulated anti-programmed death ligand 1 (PD-L1) antibody-conjugated (Lipo-anti-PD-L1-P4) evaluated effects growth MDA-MB-231 cells, PD-L1-expressing triple-negative breast cancer line, vitro NOG-hIL-4-Tg mice transplanted human peripheral blood mononuclear cells (humanized mice). Lipo-anti-PD-L1-P4 concentrations reduced proliferation . Humanized bearing expressing PD-L1 showed suppressed tumor tissue inflammation. The proportion B CD4+ decreased, whereas CD8+ increased Lipo-anti-PD-L1-P4-administrated spleens tumor-infiltrated lymphocytes. Our results suggested establishes systemic environment minimal toxicity. Thus, use as an represent strategy for treatment.

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ژورنال

عنوان ژورنال: Frontiers in Immunology

سال: 2023

ISSN: ['1664-3224']

DOI: https://doi.org/10.3389/fimmu.2023.1173728