Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4.
Details
Serval ID
serval:BIB_311C82900611
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4.
Journal
Clinical cancer research
ISSN
1078-0432
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
15
Number
7
Pages
2507-2513
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
PURPOSE: Ipilimumab is a monoclonal antibody that blocks the immune-inhibitory interaction between CTL antigen 4 (CTLA-4) and its ligands on T cells. Clinical trials in cancer patients with ipilimumab have shown promising antitumor activity, particularly in patients with advanced melanoma. Often, tumor regressions in these patients are correlated with immune-related side effects such as dermatitis, enterocolitis, and hypophysitis. Although these reactions are believed to be immune-mediated, the antigenic targets for the cellular or humoral immune response are not known. EXPERIMENTAL DESIGN: We enrolled patients with advanced melanoma in a phase II study with ipilimumab. One of these patients experienced a complete remission of his tumor. The specificity and functional properties of CD8-positive T cells in his peripheral blood, in regressing tumor tissue, and at the site of an immune-mediated skin rash were investigated. RESULTS: Regressing tumor tissue was infiltrated with CD8-positive T cells, a high proportion of which were specific for Melan-A. The skin rash was similarly infiltrated with Melan-A-specific CD8-positive T cells, and a dramatic (>30-fold) increase in Melan-A-specific CD8-positive T cells was apparent in peripheral blood. These cells had an effector phenotype and lysed Melan-A-expressing tumor cells. CONCLUSIONS: Our results show that Melan-A may be a major target for both the autoimmune and antitumor reactions in patients treated with anti-CTLA-4, and describe for the first time the antigen specificity of CD8-positive T cells that mediate tumor rejection in a patient undergoing treatment with an anti-CTLA-4 antibody. These findings may allow a better integration of ipilimumab into other forms of immunotherapy.
Keywords
Antibodies, Monoclonal/therapeutic use, Antigens, Neoplasm/immunology, Antineoplastic Agents/therapeutic use, Autoimmunity, Cytotoxicity, Immunologic, Double-Blind Method, Exanthema/chemically induced, Exanthema/immunology, Humans, Lymphocytes, Tumor-Infiltrating/immunology, Melanoma/drug therapy, Melanoma/immunology, Neoplasm Proteins/immunology, Skin Neoplasms/drug therapy, Skin Neoplasms/immunology, T-Lymphocytes, Cytotoxic/immunology, Tomography, X-Ray Computed
Pubmed
Web of science
Create date
15/01/2010 15:24
Last modification date
20/08/2019 13:16