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Clinical therapeutics

Cytotoxic T-lymphocyte antigen-4 blockade in melanoma.


PMID 25746738

Abstract

Melanoma is an aggressive malignancy that has a complex relationship with the host immune system. Immunotherapies have long been a mainstay of melanoma therapy, and advanced therapies continue to be effective in treating this disease. Immune checkpoint blockade has proven to be a novel target in melanoma, with the approval of cytotoxic T-lymphocyte antigen-4 (CTLA-4)-targeted therapy. This review evaluates the role of CTLA-4-targeted therapies in the treatment of metastatic melanoma, with a focus on mechanisms, efficacy, toxicity, and future directions of this therapy. A search was performed in PubMed to identify relevant clinical studies that explored the clinical experience with CTLA-4-targeted therapy in melanoma. Signaling through CTLA-4 causes deactivation of T cells after the initial stimulatory signals. Therapies that block CTLA-4 lead to increased T-cell function and an antitumor response in patients with metastatic melanoma. The adverse event profile of these agents is different from that seen with more traditional cancer therapies and consists of dermatitis, colitis, and other autoimmune toxicities. In addition, the pattern of response is different from that seen with traditional cytotoxic therapies, with some patients experiencing initial progression followed by response and some patients having long-term durable responses. Extensive clinical evidence supports the use of CTLA-4-targeted agents in the treatment of metastatic melanoma. The durability of response seen in patients receiving these agents has changed the landscape for patients with melanoma. Combination therapies and other agents with similar mechanisms warrant further exploration for the treatment of metastatic melanoma.