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Lack of tumor recognition by cytolytic T lymphocyte clones recognizing peptide 195-203 encoded by gene MAGE-A3 and presented by HLA-A24 molecules.

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So, Tomoko Hanagiri, Takeshi Chapiro, Jacques Colau, Didier Brasseur, Francis Coulie, Pierre G. [UCL]

Gene MAGE-A3 encodes tumor-specific antigenic peptides recognized by T cells on many tumors. MAGE-A3 peptides presented by HLA class I molecules have been identified using CD8 lymphocytes stimulated with cells that either expressed gene MAGE-A3 or were pulsed with candidate peptides. One antigen identified with the latter method is peptide MAGE-A3(195-203) IMPKAGLLI, presented by HLA-A24 molecules. It has been used to vaccinate advanced cancer patients. Here, we have used HLA/peptide tetramers to detect T cells recognizing this peptide. Their frequency was estimated to be 2 x 10(-8) of the blood CD8 cells in non-cancerous HLA-A24(+) individuals, which is tenfold lower than the reported frequencies of T cells against other MAGE peptides. In the blood of a patient vaccinated with MAGE-A3, the estimated frequency was 5 x 10(-7). Anti-MAGE-3.A24 cytolytic T cell clones were derived, that lysed peptide-pulsed cells with half-maximal effect at the low concentration of 500 pM. However, these CTL did not recognize a panel of HLA-A24(+) tumor cells that expressed MAGE-A3 at levels similar to those found in HLA-A1(+) tumor cells recognized by anti-MAGE-3.A1 CTLs. Furthermore, 293-EBNA cells transfected with MAGE-A3 and HLA-A24 constructs were hardly recognized by the anti-MAGE-3.A24 CTL clones. These results suggest that peptide MAGE-A3(195-203) is poorly processed and is not an appropriate target for cancer immunotherapy.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2007
Journal information "Cancer Immunology, Immunotherapy : other biological response modifications" - Vol. 56, no. 2, p. 259-269 (2007)
Peer reviewed yes
Publisher Springer ((Germany) Heidelberg)
issn 0340-7004
e-issn 1432-0851
Publication status Publié
Affiliation UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
MESH Subject Antigen Presentation - immunology ; Antigens, Neoplasm - genetics - immunology ; Clone Cells ; HLA-A Antigens - immunology ; Humans ; Lymphocyte Activation - immunology ; Melanoma - immunology ; Neoplasm Proteins - genetics - immunology ; Peptides - immunology ; T-Lymphocytes, Cytotoxic - immunology
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Bibliographic reference So, Tomoko ; Hanagiri, Takeshi ; Chapiro, Jacques ; Colau, Didier ; Brasseur, Francis ; et. al. Lack of tumor recognition by cytolytic T lymphocyte clones recognizing peptide 195-203 encoded by gene MAGE-A3 and presented by HLA-A24 molecules.. In: Cancer Immunology, Immunotherapy : other biological response modifications, Vol. 56, no. 2, p. 259-269 (2007)
Permanent URL http://hdl.handle.net/2078.1/10611