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

• Published in: Journal of immunotherapy (1997) Vol. 35; no. 1; p. 89
• Main Authors: Weber, Jeffrey S, Hamid, Omid, Chasalow, Scott D, Wu, Dianna Y, Parker, Susan M, Galbraith, Susan, Gnjatic, Sacha, Berman, David
• Format: Journal Article
• Language: English
• Published: United States 01.01.2012
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antigens, Neoplasm - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; 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; Ipilimumab; Lymphocyte Activation - drug effects; Male; Melanoma - drug therapy; Melanoma - immunology; Melanoma - pathology; Melanoma - physiopathology; Middle Aged; Neoplasm Staging; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Skin Neoplasms - physiopathology; Vaccines - administration & dosage
• ISSN: 1537-4513
• DOI: 10.1097/CJI.0b013e31823aa41c

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.