Optochemical Control of Immune Checkpoint Blockade via Light-Triggered PD-L1 Dimerization

The blockade of PD-1/PD-L1, which serves to release the brake of tumor immunity, represents a promising approach for treating various malignancies. However, the systemic immune-related side effects significantly undermine its therapeutic efficacy. To address this dilemma, a photoactivatable and biocompatible prodrug cBMS-1 based on the concept of photopharmacology is reported. The prodrug exhibits negligible toxicity but exerts effective PD-1/PD-L1 axis inhibition upon light irradiation, holding promising potential to achieve local activation of immune responses in clinical settings.

Automated summary

Blockading PD-1/PD-L1 has the potential to be a promising approach for treating malignancies, but its systemic immune-related side effects reduce its therapeutic efficacy. To address this issue, a photoactivatable and biocompatible prodrug cBMS-1 based on the concept of photopharmacology has been developed. The prodrug exhibits minimal toxicity but effectively inhibits the PD-1/PD-L1 axis upon light irradiation, offering promising potential for locally activating immune responses in clinical settings.