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    For Research Use Only. Not For Clinical Use.


    Background

    Every year, thousands of dogs are diagnosed with cancer. Canine cancers share many of the characteristics of human cancers, including tissue location, tumor progression, and response to chemotherapy and radiation. Unfortunately, the canine lymphocyte population is not as well defined as human lymphocytes, and reagents targeting the immune checkpoint pathway have not been widely used in veterinary research. Interruption of the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is an established and effective therapeutic strategy in human oncology and may also be effective in the treatment of canine cancers.
    Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is an immune checkpoint receptor expressed on activated T cells and regulatory T cells (Tregs). It competes with CD28 for binding to B7 ligands (CD80/CD86) on antigen-presenting cells (APCs), suppressing T cell activation and limiting immune responses to self-antigens. Tumors exploit CTLA4 to evade anti-tumor immunity. Monoclonal antibodies blocking CTLA4 (ipilimumab, tremelimumab) enhance T cell activation and expansion, unleashing anti-tumor immunity. Approved for melanoma, renal cell carcinoma (RCC), and colorectal cancer, CTLA4 inhibitors are often combined with PD-1/PD-L1 blockers for synergistic efficacy.
    CTLA4 & PD-1
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