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

• DOI: 10.3389/fimmu.2023.1173728
• Publication Date: 2023-07-10T09:22:48Z
• Authors: Yoshie Kametani; Ryoji Ito; Shino Ohshima; Yoshiyuki Manabe; Yusuke Ohno; Tomoka Shimizu; Soga Yamada; Nagi Katano; Daiki Kirigaya; Keita Ito; Takuya Matsumoto; Banri Tsuda; Hirofumi Kashiwagi; Yumiko Goto; Atsushi Yasuda; Masatoshi Maeki; Manabu Tokeshi; Toshiro Seki; Koichi Fukase; Mikio Mikami; Kiyoshi Ando; Hitoshi Ishimoto; Takashi Shiina
• Keywords: Systemic administration

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.