CTLA-4 Antibodies 

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), also known as CD152, is an immune checkpoint receptor expressed primarily on activated T cells and regulatory T cells (Tregs). CTLA-4 competes with the co-stimulatory receptor CD28 for binding to its ligands, B7-1 (CD80) and B7-2 (CD86), thereby downregulating T cell activation and proliferation. This inhibitory mechanism is crucial for maintaining immune homeostasis but is exploited by tumors to evade immune surveillance. 

Content and Structural Features of CTLA-4 Antibodies

CTLA-4 antibodies are monoclonal immunoglobulins (IgG) that disrupt CTLA-4/B7 interactions, restoring immune activation by facilitating CD28-mediated costimulation.

Key CTLA-4 Antibodies

1. Ipilimumab (Yervoy®): A fully human IgG1 mAb that blocks CTLA-4, enhancing T cell activation and proliferation.
2. Tremelimumab: An investigational IgG2 mAb targeting CTLA-4, currently studied in various cancers, including mesothelioma and hepatocellular carcinoma.

Applications in Immunotherapy

CTLA-4 antibodies have been extensively investigated in oncology and are also being explored in autoimmune and infectious disease settings.

1. Oncology

CTLA-4 inhibitors have demonstrated significant clinical benefit in:

• Melanoma: Ipilimumab was the first checkpoint inhibitor approved for metastatic melanoma, either as monotherapy or in combination with PD-1 inhibitors such as nivolumab.
• Non-Small Cell Lung Cancer (NSCLC): Used in combination with PD-1 blockade for enhanced efficacy.
• Renal Cell Carcinoma (RCC): Combination regimens with PD-1 inhibitors improve survival outcomes.
• Hepatocellular Carcinoma (HCC): Investigated in combination immunotherapy approaches.

2. Autoimmune and Infectious Diseases

• Chronic infections: Potential applications in chronic viral infections where T cell exhaustion limits immune response.
• Autoimmune diseases: CTLA-4 pathway modulation is being explored for conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis.

CTLA-4 antibodies represent a key class of immune checkpoint inhibitors that enhance T cell activation and proliferation by blocking inhibitory signals at the antigen-presenting cell level. Their use in combination with PD-1/PD-L1 inhibitors has demonstrated superior efficacy in multiple cancers.