Ipilimumab increases activated T cells and enhances humoral immunity in patients with advanced melanoma

  • Weber J
  • Hamid O
  • Chasalow S
 et al. 
  • 21

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Abstract

Ipilimumab, a fully human monoclonal antibody, which blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in 2 phase III trials of patients with advanced melanoma. To gain an understanding of its mechanism of action, the effects of ipilimumab on T-cell populations and on humoral immune responses were studied in patients with advanced melanoma from 2 phase II trials. Antibody levels against 5 tumor antigens were assessed at baseline and up to 12 weeks after ipilimumab treatment. Serologic reactivity to the cancer-testis antigen NY-ESO-1 increased by at least 5-fold at week 12 of treatment in 10% to 13% of patients. Increased antibody levels were also observed to the tumor antigens Melan-A, MAGE-A4, SSX2, and p53. Immunocompetence was evaluated with tetanus boosters administered before ipilimumab and pneumococcal and influenza vaccines given 5 days after ipilimumab treatment. At week 7, most patients who received ipilimumab and vaccine showed greater humoral responses relative to baseline titers. For peripheral T-cell populations, statistically significant increases in the percent of activated (HLA-DR) CD4 and CD8 T cells with concomitant decreases in naive CD4 and CD8 T cells were observed after ipilimumab treatment. These changes were evident by week 4 of treatment. Increases were also observed in central memory, effector memory, and activated ICOS CD4 T cells, but not in ICOS CD8 T cells or in FoxP3 CD4 regulatory T cells. These results suggest that ipilimumab can enhance immune responses mediated by different T-cell populations, and humoral immunity, in melanoma patients.

Author-supplied keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal/*administration & dosage/ad
  • Antigens, Neoplasm/immunology
  • CD4-Positive T-Lymphocytes/drug effects/immunology
  • CD8-Positive T-Lymphocytes/drug effects/immunology
  • Cell Count
  • Disease Progression
  • Female
  • Follow-Up Studies
  • HLA-DR Antigens/metabolism
  • Humans
  • Immunity, Humoral/drug effects
  • Immunocompetence/drug effects
  • Immunologic Memory/drug effects
  • Inducible T-Cell Co-Stimulator Protein/metabolism
  • Lymphocyte Activation/drug effects
  • Male
  • Melanoma/*drug therapy/*immunology/pathology/physi
  • Middle Aged
  • Neoplasm Staging
  • Skin Neoplasms/*drug therapy/*immunology/pathology
  • Vaccines/administration & dosage

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Authors

  • J S Weber

  • O Hamid

  • S D Chasalow

  • D Y Wu

  • S M Parker

  • S Galbraith

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