Enhanced magnetic hyperthermia using anti-PD-L1 antibody-conjugated magnetoliposomes in a murine subcutaneous bladder cancer model.

Abstract

BACKGROUND/OBJECTIVES: Bladder cancer (BC) often arises in an immunosuppressive tumor microenvironment that limits responses to immune checkpoint inhibitors. Magnetic hyperthermia therapy (MHT) can induce immunogenic cell death, but its value as an immunotherapeutic remains insufficient. METHODS: We conjugated anti-programmed death-ligand 1 (PD-L1) antibody (αPD-L1) with magnetite cationic liposomes (MCL) and developed αPD-L1@MCL for MHT in an MB49 murine subcutaneous BC model. Mice received a single or triple exposure of αPD-L1@MCL-mediated MHT (P-MHT) at 43 °C or 46 °C ( = 5 per group), then we assessed tumor growth and CD8T-cell infiltration. RESULTS: Without αPD-L1, triple MHT at 46 °C induced complete tumor regression, whereas a single exposure 43 °C was insufficient. A single exposure 43 °C P-MHT achieved complete regression in four out of five mice. Flow cytometry revealed an increase in CD8T cells in tumors treated with P-MHT. CONCLUSIONS: Our αPD-L1@MCL enables hyperthermia with magnetic nanoparticles and immunotherapy with an anti-PD-L1 antibody. These findings support further development of hyperthermia mediated by anti-PD-L1 antibody-conjugated magnetic nanoparticles as a promising therapeutic strategy for BC.