Peptide blockers of PD-1-PD-L1 Interaction Reinvigorate PD-1-supressed T Cells and Curb Tumor Growth in Mice

Background

T cell function is regulated by a balance between activating and inhibitory signals, the latter of which includes those mediated by immune checkpoints. Of note, the binding programmed cell death 1 (PD‑1) by its ligand (PD‑L1) triggers a co‑inhibitory signaling pathway that suppresses T cell activation, contributing to cancer immune evasion.

While monoclonal antibodies that block PD-1 or PD-L1 have revolutionized the treatment of certain cancers such as melanoma and non‑small cell lung cancer, they have yielded less favorable outcomes for other cancers such as cancers of the breast, colon, and pancreas. Such therapies are also expensive to produce and can lead to immune-related side effects. As such, this necessitates alternative approaches to enhance treatment outcomes across a broader spectrum of malignancies.

Technology Overview

Researchers at Western University have developed a novel approach to blocking the PD-1/PD-L1 interaction using peptide‑based inhibitors as an alternative means to PD‑1/PD‑L1 blockade antibodies for anti‑cancer immunotherapy. Developed through a rigorous process of functional screening and optimization, mL7N is a 16-mer peptide engineered for enhanced solubility, stability, and bioactivity. Initial studies demonstrate mL7N’s ability to disrupt the PD-1/PD-L1 interaction both in vitro and in vivo, effectively rejuvenating PD-1-suppressed T cells and inhibit tumor growth in mice by promoting tumor recruitment of CD8+ T cells.

By targeting the PD-1/PD-L1 axis with peptides, this technology opens new avenues for developing safer and more accessible immunotherapies capable of overcoming current limitations in cancer treatment efficacy and safety.

Benefits

• Cost-effective production compared to monoclonal antibodies.
• Reduced risk of immune-related adverse events.
• Improved bioavailability and tissue penetration.

Applications

• Novel line of immunotherapeutic agents for cancer treatment.
• Treatment of cancers that are not responsive to current PD-1/PD-L1 antibody therapies.

Opportunity

• Licensing