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

J Immunother. Nov-Dec 2004;27(6):478-9. doi: 10.1097/00002371-200411000-00008.

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.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD
  • Antigens, Differentiation / immunology*
  • Autoimmune Diseases / immunology
  • CTLA-4 Antigen
  • Female
  • Humans
  • Male
  • Melanoma / complications*
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Neoplasm Staging
  • T-Lymphocytes, Cytotoxic / immunology
  • Uvea / pathology
  • Uveitis / immunology*
  • gp100 Melanoma Antigen

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • gp100 Melanoma Antigen