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© Research
Publication : Clinical cancer research : an official journal of the American Association for Cancer Research

Immunogenic HLA-B*0702-restricted epitopes derived from human telomerase reverse transcriptase that elicit antitumor cytotoxic T-cell responses

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Clinical cancer research : an official journal of the American Association for Cancer Research - 15 May 2006

Adotévi O, Mollier K, Neuveut C, Cardinaud S, Boulanger E, Mignen B, Fridman WH, Zanetti M, Charneau P, Tartour E, Lemonnier F, Langlade-Demoyen P

Link to Pubmed [PMID] – 16707616

Clin. Cancer Res. 2006 May;12(10):3158-67

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.

http://www.ncbi.nlm.nih.gov/pubmed/16707616