Immune Checkpoint Blockade Mediated by a Small ‐Molecule Nanoinhibitor Targeting the PD‐1/PD‐L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer

Photodynamic therapy induces apoptosis and necrosis of 4T1 tumor cells, leading to the release of tumor ‐associated antigens. Matured dendritic cells migrate to the lymph node to activate T cells which infiltrate to the tumor cells. Small‐molecule inhibitor BMS‐202 acts through programmed death ligand 1 (PD‐L1) dimerization to block the activity of PD‐L1 proteins thus restoring T cell functi on. AbstractTargeting 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, Brist ol‐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 BM S. 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 anti tumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen‐specific T cells int...
Source: Small - Category: Nanotechnology Authors: Tags: Communication Source Type: research