title: Ipilimumab increases activated T cells and enhances humoral immunity in patients with advanced melanoma.
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.
authors: Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA. Jeffrey.Weber@moffitt.org
authors: Jeffrey S
authors: JS
authors: Weber
authors: Omid
authors: O
authors: Hamid
authors: Scott D
authors: SD
authors: Chasalow
authors: Dianna Y
authors: DY
authors: Wu
authors: Susan M
authors: SM
authors: Parker
authors: Susan
authors: S
authors: Galbraith
authors: Sacha
authors: S
authors: Gnjatic
authors: David
authors: D
authors: Berman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007121:Immunocompetence / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D000074324:Ipilimumab; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D014612:Vaccines / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006684:HLA-DR Antigens; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D000074324:Ipilimumab; D014612:Vaccines