The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications

Semin Oncol. 2010 Oct;37(5):499-507. doi: 10.1053/j.seminoncol.2010.09.007.


The promising new class of immunomodulating antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) has been extensively tested in clinical trials and found to be active against cutaneous melanoma and other tumor histotypes. Inhibition of CTLA-4 characteristically induces well-identified side effects for which the definition "immune-related adverse events" (irAEs) has been proposed. IrAEs mainly include colitis/diarrhea, dermatitis, hepatitis, and endocrinopathies; uveitis, nephritis, and inflammatory myopathy also have been reported occasionally. These unique side effects are likely a direct result of breaking immune tolerance upon CTLA-4 blockade and are generally mild, reversible, and manageable, following specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. However, patient-physician communication and early treatment are also emerging as critical issues to successfully manage irAEs, thus avoiding major complications. The major experience in identifying and managing CTLA-4 treatment-related side effects has derived from studies in melanoma patients; nevertheless, accumulating clinical experiences are clearly demonstrating that irAEs are class-specific events, and that they are fully overlapping in patients with tumors of different histotypes. This review provides an overview of current safety data on CTLA-4 antagonists and of available strategies to optimize their clinical use in cancer patients.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD / immunology*
  • Antineoplastic Agents / adverse effects*
  • CTLA-4 Antigen
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / therapy
  • Drug-Related Side Effects and Adverse Reactions
  • Endocrine System Diseases / chemically induced
  • Endocrine System Diseases / immunology
  • Endocrine System Diseases / therapy
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / immunology
  • Gastrointestinal Diseases / therapy
  • Humans
  • Immune System Diseases / chemically induced*
  • Ipilimumab
  • Melanoma / drug therapy
  • Skin Diseases / chemically induced
  • Skin Diseases / immunology
  • Skin Diseases / therapy
  • Skin Neoplasms / drug therapy


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antineoplastic Agents
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ipilimumab
  • tremelimumab