Releasing the Brake on the Immune System: Ipilimumab in Melanoma and Other Tumors

  • Tarhini A
  • Lo E
  • Minor D
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Abstract

Advanced melanoma has proven difficult to treat for many years, and no previous agent has shown improved survival in a phase 3 trial. The deepening understanding of tumor immunobiology and the complexity of the interactions between host T cells and cancer have led to novel treatment approaches. Among these, ipilimumab is a first-in-class T-cell potentiator that works by blocking cytotoxic T-lymphocyte antigen-4, a critical negative regulator of the antitumor T-cell response. From phase 1 studies, ipilimumab has shown encouraging activity in melanoma and other cancers, with unusual response patterns and mechanism-related, predictable toxicities that are medically manageable and mostly reversible but can sometimes be life threatening unless recognized and treated early. Early indications of a survival benefit in phase 2 studies have been confirmed recently in the first randomized phase 3 trial; the primary endpoint of the trial, overall survival (OS), was met with ipilimumab significantly prolonging median OS both as a single agent (10.1 months; p = 0.003) and combined with gp100 vaccine (10.0 months; p 

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Authors

  • Ahmad Tarhini

  • Ernest Lo

  • David R. Minor

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