Targeting
programmed cell death protein 1 (PD-1)/
programmed death ligand 1 (PD-L1) immunologic checkpoint blockade with
monoclonal antibodies has achieved recent clinical success in antitumor
therapy. However, therapeutic
antibodies exhibit several issues such as limited
tumor penetration, immunogenicity, and costly production. Here, Bristol-Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS-202 is a small-molecule inhibitor of the PD-1/PD-L1 interaction that is developed by BMS. Transfer of BMS-202 NPs to 4T1
tumor-bearing mice results in markedly slower
tumor growth to the same degree as treatment with anti-PD-L1
monoclonal antibody (α-PD-L1). Consistently, the combination of Ce6 NPs with BMS-202 NPs or α-PD-L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of
antigen-specific T cells into the
tumors. Thus, inhibition rates of primary and distant
tumors reach >90%. In addition, BMS-202 NPs are able to attack spreading metastatic lung
tumors and offer immune-memory protection to prevent
tumor relapse. These results indicate that BMS-202 NPs possess effects similar to α-PD-L1 in the
therapies of 4T1
tumors. Therefore, this work reveals the possibility of replacing the antibody used in
immunotherapy for
tumors with BMS-202 NPs.