This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Adotévi, O. Articles by Langlade-Demoyen, P. Search for Related Content PubMed PubMed Citation Articles by Adotévi, O. Articles by Langlade-Demoyen, P.

Immunogenic HLA-B*0702-Restricted Epitopes Derived from Human Telomerase Reverse Transcriptase That Elicit Antitumor Cytotoxic T-Cell Responses

Authors' Affiliations: ¹ Institut National de la Sante et de la Recherche Medicale U255, Université René Descartes, Unité d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Assistance-Public Hôpitaux de Paris; ² Unité de Virologie Moléculaire and ³ Unité d' Oncogenèse et Virologie Moléculaire, Institut National de la Sante et de la Recherche Medicale U579 and ⁴ Immunité Cellulaire Antivirale, Institut Pasteur, Paris, France; ⁵ Etablissement Français du Sang, site Hôpital Henri Mondor, Assistance-Public Hôpitaux de Paris, Créteil, France; and ⁶ Department of Medicine and Cancer Center, University of California at San Diego, La Jolla, California

Requests for reprints: Olivier Adotévi, Hôpital Européen Georges Pompidou, Assistance-Public Hôpitaux de Paris, 20 rue Leblanc, 75908 Paris Cedex 15, France. Phone: 33-56-09-39-80; Fax: 33-56-09-20-80; E-mail: Olivier.adotevi{at}hop.egp.ap-hop-paris.fr.

Purpose: The human telomerase reverse transcriptase (hTERT) is considered as a potential target for cancer immunotherapy because it is preferentially expressed in tumor cells. To increase the applicability of hTERT-based immunotherapy, we set out to identify CTL epitopes in hTERT restricted by HLA-B*0702 molecule, a common MHC class I allele.

Experimental Design: HLA-B*0702-restricted peptides from hTERT were selected by using a method of epitope prediction and tested for their immunogenicity in human (in vitro) and HLA-B*0702 transgenic mice (in vivo).

Results: All the six hTERT peptides that were predicted to bind to HLA-B*0702 molecule were found to induce primary human CTL responses in vitro. The peptide-specific CD8⁺ CTL lines were tested against various hTERT⁺ tumor cells. Although differences were observed according to the tumor origin, only three CTL lines specific for p277, p342, and p351 peptides exhibited cytotoxicity against tumor cells in a HLA-B*0702-restricted manner. In addition, this cytotoxicity was inhibited by the addition of peptide-loaded cold target cells and indicated that these epitopes are naturally processed and presented on the tumor cells. Further, in vivo studies using humanized HLA-B*0702 transgenic mice showed that all the candidate peptides were able to induce CTL responses after peptide immunization. Furthermore, vaccination with a plasmid DNA encoding full-length hTERT elicited peptide-specific CTL responses, indicating that these epitopes are efficiently processed in vivo.

Conclusions: Together with previously reported hTERT epitopes, the identification of new CTL epitopes presented by HLA-B*0702 increases the applicability of hTERT-based immunotherapy to treating cancer.