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

Abstract

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.

Light-Activated Azobenzene Peptide Inhibitor of the PD-1/PD-L1 Interaction

“…The IC50 of the restored inhibitory effect following light irradiation was 1.032 µM. 41 The approach demonstrated here has improved this proof-of-concept by an order of magnitude and offers great promise in the development of photo-controlled inhibitors of PD-1/PD-L1.…”

Visible light degradable micelles for intraocular corticosteroid delivery

“…The observed cytotoxicity of the micelles and their degradation products at high concentration was likely caused by the cleaved DEACM as the degradation products of P(TMC- ran -HTMC) have been shown to be noncytotoxic up to 2 mg mL −1 24 while DEACM showed some cytotoxicity above 80 μM. 35…”

Light-activated azobenzene peptide inhibitor of the PD-1/PD-L1 interaction

“…The IC 50 of the restored inhibitory effect following light irradiation was 1.032 μM. 46 The approach demonstrated here has improved this proof-of-concept by an order of magnitude and offers great promise in the development of photo-controlled inhibitors of PD-1/PD-L1.…”