CTLA4抗体—艾普蒂

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     The image is immunohistochemistry of paraffin-embedded Human colorectal cancer tissue using P10781(CTLA4 Antibody) at dilution 1/20. (Original magnification: ×200)    

  
  

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     The image is immunohistochemistry of paraffin-embedded Human thyroid cancer tissue using P10781(CTLA4 Antibody) at dilution 1/20. (Original magnification: ×200)    

  
  

CTLA4 (cytotoxic T-lymphocyte-associated antigen 4), a critical immune checkpoint protein, was first identified in the 1980s as a homolog of CD28. It is primarily expressed on regulatory T cells (Tregs) and activated T cells, functioning as a negative regulator of T-cell activation. Unlike CD28. which provides co-stimulatory signals upon binding to B7 molecules (CD80/CD86) on antigen-presenting cells (APCs), CTLA4 exhibits higher affinity for B7 ligands, competitively inhibiting CD28-B7 interactions and suppressing early T-cell activation in lymphoid organs. This mechanism prevents excessive immune responses and maintains self-tolerance.

In the mid-1990s, James Allison’s groundbreaking work demonstrated that blocking CTLA4 with antibodies enhanced antitumor immunity in preclinical models. This led to the development of ipilimumab, the first FDA-approved CTLA4 inhibitor (2011), for metastatic melanoma. By disrupting CTLA4-mediated inhibitory signals, these antibodies promote T-cell proliferation and tumor infiltration, though often triggering immune-related adverse events due to widespread immune activation. Despite modest response rates as monotherapy, CTLA4 inhibitors laid the foundation for cancer immunotherapy, particularly in combination with PD-1/PD-L1 blockers, improving outcomes in multiple cancers. Research continues to optimize dosing, minimize toxicity, and identify predictive biomarkers to refine clinical applications.