Emerging targets for anticancer vaccination: PD-1.

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Tumor cells evade immune surveillance partly through the programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) interaction.
• Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway with monoclonal antibodies have advanced cancer therapy but face limitations such as limited efficacy, frequent administration, and high costs.

Purpose of the Study:

• To review recent developments in using small molecules and peptides to overcome limitations of current PD-1/PD-L1 pathway inhibitors.
• To explore peptide-based strategies for blocking PD-1/PD-L1 interactions and for active immunization to enhance anti-tumor immunity.

Main Methods:

• Review of literature on small molecules and peptides targeting the PD-1/PD-L1 pathway.
• Analysis of peptide-based active immunization strategies for cancer therapy.

Main Results:

• Small peptides can directly interfere with PD-1/PD-L1 interactions, offering an alternative to antibodies.
• Peptides derived from PD-1 or PD-L1 sequences can be used in vaccination approaches to induce antibodies that block PD-1-mediated T-cell inhibition.
• Combining cancer antigen peptides with PD-1/PD-L1 blocking peptides can enhance anti-tumor immune responses.

Conclusions:

• Small molecules and peptides represent promising alternatives to antibody-based ICIs for cancer treatment.
• Peptide-based vaccines hold potential for inducing robust anti-tumor immunity by modulating the PD-1/PD-L1 pathway.