Tumor Regression and Autoimmunity in CytotoxicT Lymphocyte–Associated Antigen 4 Blockade–Treated Patients
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Progress in cancer immunotherapy has been modest in the last two decades since interleukin (IL)-2 was shown to induce long-term sustained responses in a proportion of patients with melanoma and renal cell cancer.1,2 That cytokine was approved in the late 1990s by the US Food and Drug Administration for the treatment of stage IV renal cell cancer and melanoma. The exact mechanism of action by which IL-2 mediates regression of melanoma is unknown. Various empiric combinations of agents active in melanoma have been tested with IL-2, including chemotherapy agents and other cytokines,3,4 without a clear benefit in overall survival. The article by Maker et al.5 in this issue of Annals of Surgical Oncology describes a study of immunotherapy with high-dose IL-2 combined with a novel antibody that abrogates the effects of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) in patients with stage IV melanoma.6The CTLA-4 molecule is expressed on activated T cells and competes with coactivator...
KeywordsMelanoma Renal Cell Cancer Peptide Vaccine Small Pilot Trial Autoimmune Toxicity
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