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

Jeffrey S. Weber, Omid Hamid, Scott D. Chasalow, Dianna Y. Wu, Susan M. Parker, Susan Galbraith, Sacha Gnjatic, David Berman

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

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.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalJournal of Immunotherapy
Volume35
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • T-cell populations
  • cytotoxic T-lymphocyte antigen-4
  • humoral immunity
  • ipilimumab
  • melanoma

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