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
Author(s)
Klein O., Ebert L.M., Nicholaou T., Browning J., Russell S.E., Zuber M., Jackson H.M., Dimopoulos N., Tan B.S., Hoos A., Luescher I.F., Davis I.D., Chen W., Cebon J.
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
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
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