[Anti-PD-1 antibody: basics and clinical application]

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Context:

• T cell-directed cancer immunotherapy has historically faced challenges.
• The programmed cell death protein 1 (PD-1) pathway is a key regulator of T cell responses.
• PD-1, expressed on T cells, interacts with ligands PD-L1 and PD-L2 to deliver coinhibitory signals.

Purpose:

• To review the role of the PD-1 signaling pathway in cancer immunity.
• To evaluate the therapeutic potential of blocking PD-1/PD-L1 interactions in cancer treatment.
• To compare the safety and efficacy of PD-1 blockade with CTLA-4 blockade.

Summary:

• The PD-1/PD-L1 system plays a critical role in regulating immune responses, including those against tumors.
• Anti-PD-1 and anti-PD-L1 monoclonal antibodies offer a targeted approach to augment T cell responses to cancer.
• Phase I trials demonstrated objective responses in patients with melanoma, renal cell carcinoma, and non-small cell lung cancer treated with anti-PD-1 antibodies, and antitumor activity with anti-PD-L1 in several cancer types.

Impact:

• PD-1 axis-targeted immunotherapies represent a significant advancement in cancer treatment.
• These therapies may offer a more favorable safety profile compared to CTLA-4 inhibition due to targeting the effector phase of T cell responses.
• Future research directions include defining patient selection criteria and exploring combination therapies for enhanced antitumor activity.