Design of an Injectable Polypeptide Hydrogel Depot Containing the Immune Checkpoint Blocker Anti-PD-L1 and Doxorubicin to Enhance Antitumor Combination Therapy.

Abstract

Combination therapy can be used to enhance the therapeutic response and decrease side effects during cancer treatment. In this study, a system is developed to locally deliver the immune checkpoint blockade antibody targeting programmed death-ligand 1 (anti-PD-L1 or aPD-L1) and doxorubicin (Dox), by an injectable, biocompatible polypeptide hydrogel as a drug depot. The localized and sustained release of Dox after the intratumoral injection of the co-loaded hydrogel induces immunogenic tumor cell death, thus promoting an antitumor immunological response. The tumor inhibitory effect is significantly enhanced by the simultaneous release of aPD-L1 at the tumor site thanks to its action on the inhibition of the PD-1/PD-L1 pathway and restoration of the tumor-killing effect of cytotoxic T cells. Treatment of the B16F10 melanoma model with the aPD-L1 and Dox co-loaded hydrogel leads to a remarkable inhibition of tumor progression and prolongation of animal survival.