J Immunother. 2004 Nov-Dec;27(6):478-9.

Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis.

Robinson MR, Chan CC, Yang JC, Rubin BI, Gracia GJ, Sen HN, Csaky KG, Rosenberg SA.

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National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1863, USA. robinsonm@nei.nih.gov

Abstract

Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) is an important costimultory receptor expressed on activated T cells. CTLA-4 blockade using a monoclonal antibody (mAb) in conjunction with tumor vaccines has improved tumor responses in animal models and enhanced numerous models of T cell-associated autoimmune diseases. Two patients with stage IV metastatic melanoma vaccinated with the gp 100 melanocyte/melanoma differentiation antigen either before or during anti-CTLA-4 mAb therapy developed uveitis. This is the first report of autoimmune disease involving the eye in patients treated with anti-CTLA-4 mAb. This suggests that CTLA-4 is an important regulatory molecule for maintenance of tolerance to melanosomal antigens and prevention of uveitis.

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