Development of a Peptide-Based Photoimmunotherapy Drug Targeting PD-L1.

Area of Science:

• Oncology
• Immunotherapy
• Bioconjugation

Background:

• Near-infrared photoimmunotherapy (NIR-PIT) offers selective cancer treatment.
• Current NIR-PIT relies on a single antibody-based drug, necessitating exploration of alternative therapeutic agents.
• Programmed death-ligand 1 (PD-L1) is overexpressed in various cancers, making it a viable therapeutic target.

Purpose of the Study:

• To develop and evaluate a novel peptide-based drug for PD-L1-targeted NIR-PIT.
• To assess the efficacy of the peptide-drug conjugate in vitro and in vivo.

Main Methods:

• Conjugation of the PD-L1-binding peptide WL12 with the photoabsorber IRDye700DX (IR700).
• In vitro evaluation of WL12-IR700 efficacy on PD-L1-positive cancer cells under NIR light irradiation.
• In vivo assessment of tumor growth suppression and survival rates in preclinical cancer models.

Main Results:

• WL12-IR700 induced photoimmunotherapy-like cell death in PD-L1-positive cancer cells.
• Cancer cell viability was reduced in a dose- and concentration-dependent manner.
• Significant tumor growth suppression and extended overall survival were observed in vivo.

Conclusions:

• The developed peptide-based drug, WL12-IR700, is effective for PD-L1-targeted NIR-PIT.
• This peptide-drug conjugate represents a promising alternative therapeutic modality for PD-L1-expressing cancers.