title: Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis.
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.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1863, USA. robinsonm@nei.nih.gov
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Rubin
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gracia
authors.forename: H Nida
authors.initials: HN
authors.lastname: Sen
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D060908:CTLA-4 Antigen; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D009367:Neoplasm Staging; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014602:Uvea / Q000473:pathology; D014605:Uveitis / Q000276:immunology*; D058951:gp100 Melanoma Antigen
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen