EphA2 as target of anticancer immunotherapy: identification of HLA-A*0201-restricted epitopes

Détails

ID Serval
serval:BIB_48BA8C3D2D81
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
EphA2 as target of anticancer immunotherapy: identification of HLA-A*0201-restricted epitopes
Périodique
Cancer Research
Auteur⸱e⸱s
Alves  P. M., Faure  O., Graff-Dubois  S., Gross  D. A., Cornet  S., Chouaib  S., Miconnet  I., Lemonnier  F. A., Kosmatopoulos  K.
ISSN
0008-5472 (Print)
Statut éditorial
Publié
Date de publication
12/2003
Volume
63
Numéro
23
Pages
8476-80
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 1
Résumé
EphA2 (Eck) is a tyrosine kinase receptor that is overexpressed in several human cancers such as breast, colon, lung, prostate, gastric carcinoma, and metastatic melanoma but not in nonmalignant counterparts. To validate EphA2 as a tumor antigen recognized by CD8+ T lymphocytes, we used reverse immunology approach to identify HLA-A*0201-restricted epitopes. Peptides bearing the HLA-A*0201-specific anchor motifs were analyzed for their capacity to bind and stabilize the HLA-A*0201 molecules. Two peptides, EphA2(58) and EphA2(550), with a high affinity for HLA-A*0201 were selected. Both peptides were immunogenic in the HLA-A*0201-transgenic HHD mice. Interestingly, peptide-specific murine CTLs cell lines responded to COS-7 cells coexpressing HLA-A*0201 and EphA2 and to EphA2-positive human tumor cells of various origin (renal cell, lung, and colon carcinoma and sarcoma). This demonstrates that EphA2(58) and EphA2(550) are naturally processed from endogenous EphA2. In addition, EphA2(58) and EphA2(550) stimulated specific CD8(+) T cells from healthy donor peripheral blood mononuclear cells. These T cells recognized EphA2-positive human tumor cells in an HLA-A*0201-restricted manner. Interestingly, EphA2-specific CD8+ T cells were detected in the peripheral blood mononuclear cells of prostate cancer patients. These results show for the first time that EphA2 is a tumor rejection antigen and lead us to propose EphA2(58) and EphA2(550) peptides for a broad-spectrum-tumor immunotherapy.
Mots-clé
Animals CD8-Positive T-Lymphocytes/immunology COS Cells Cell Line, Tumor Cercopithecus aethiops Epitope Mapping Epitopes, T-Lymphocyte/immunology HLA-A Antigens/*immunology Immunotherapy/*methods Lymphocyte Activation/immunology Mice Mice, Transgenic Neoplasms/enzymology/immunology/*therapy Peptide Fragments/*immunology/pharmacology Receptor, EphA2/*immunology T-Lymphocytes, Cytotoxic/immunology
Pubmed
Web of science
Création de la notice
25/01/2008 16:08
Dernière modification de la notice
20/08/2019 14:55
Données d'usage