PD-1 Antibodies 

Programmed Cell Death Protein 1 (PD-1), also known as CD279, is a critical immune checkpoint receptor expressed on T cells, B cells, and natural killer (NK) cells. PD-1 functions as a negative regulator of immune activation by binding to its ligands, PD-L1 and PD-L2, which are upregulated in various tumor microenvironments. 

Content and Structural Features of PD-1 Antibodies

PD-1 antibodies are engineered monoclonal immunoglobulins (IgG) designed to competitively inhibit PD-1/PD-L1 interactions, enhancing T cell function. Structurally, they consist of a variable domain recognizing PD-1 and a constant Fc region, which may influence immune effector functions.

Key PD-1 Antibodies

• Nivolumab (Opdivo®): A fully human IgG4 mAb with a hinge-stabilized structure to minimize antibody-dependent cytotoxicity.
• Pembrolizumab (Keytruda®): A humanized IgG4 mAb with similar immune checkpoint inhibition properties.
• Cemiplimab (Libtayo®): A fully human IgG4 antibody with high affinity for PD-1, used in certain cutaneous malignancies.

Applications in Immunotherapy

PD-1 antibodies have been extensively utilized in treating solid tumors, hematological malignancies, and autoimmune diseases. Their applications include:

Oncology: PD-1 inhibitors have significantly improved survival in various cancers by enhancing T cell-mediated cytotoxicity. They are approved for:

• Non-Small Cell Lung Cancer (NSCLC): Monotherapy or in combination with chemotherapy.
• Melanoma: First-line treatment for advanced/metastatic disease.
• Hodgkin's Lymphoma: Effective in relapsed/refractory cases, particularly after autologous stem cell transplantation.
• Gastrointestinal Cancers: Approved for MSI-high colorectal cancers and certain gastric cancers.

Autoimmune and Infectious Diseases: While primarily utilized in oncology, PD-1 blockade has shown potential in:

• Chronic infections (e.g., HIV, hepatitis B, and tuberculosis) by reinvigorating exhausted T cells.
• Autoimmune disorders: Experimental applications in systemic lupus erythematosus (SLE) and type 1 diabetes by modulating T cell tolerance.

PD-1 antibodies represent a paradigm shift in immunotherapy, particularly for cancer treatment. Their efficacy in reinvigorating exhausted T cells has dramatically improved outcomes in multiple malignancies. Ongoing research focuses on expanding indications, optimizing combination therapies, and mitigating immune-related adverse effects (irAEs) such as pneumonitis, colitis, and endocrinopathies.