From monoclonal antibodies to small molecules: the development of inhibitors targeting the PD-1/PD-L1 pathway

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Cancer immunotherapy has advanced significantly, with PD-1/PD-L1 pathway blockade emerging as a key strategy.
• The PD-1/PD-L1 interaction is crucial for immune evasion in cancer and chronic viral infections.

Purpose of the Study:

• To review the development of therapeutic agents targeting the PD-1/PD-L1 pathway.
• To discuss the potential of monoclonal antibodies, peptides, and small molecules in treating cancer and virological diseases.
• To provide insights into PD-1/PD-L1 interactions for rational drug design.

Main Methods:

• Review of approved and clinically investigated monoclonal antibodies (mAbs) against PD-1/PD-L1.
• Analysis of developed peptides and small molecules targeting the PD-1/PD-L1 pathway.
• Discussion of the underlying mechanisms of PD-1/PD-L1 interactions.

Main Results:

• Several mAbs targeting the PD-1/PD-L1 pathway are approved or in clinical trials for various cancers.
• Peptides and small molecules targeting this pathway have also been developed, with potential applications beyond oncology.
• Understanding PD-1/PD-L1 interactions is critical for designing effective small-molecule inhibitors.

Conclusions:

• Further approval of mAbs for PD-1/PD-L1 pathway blockade in diverse cancers is anticipated.
• Development and clinical translation of small molecules and peptides targeting this pathway may face greater challenges.
• The PD-1/PD-L1 pathway remains a critical target for novel immunotherapeutic strategies.