NDLI: Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of tumor cells.

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Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of tumor cells.

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Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of tumor cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Langlade-demoyen, Pierre Garcia-pons, Francisco Zanetti, Maurizio Hernandez, Javier Firat, Huseyin Schmidt, Joseph D. Lone, Yu Chun
Description	Author Affiliation: Hernandez J ( Department of Medicine and Cancer Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0837, USA.);
Abstract	Telomerase reverse transcriptase (TRT) is a tumor-associated antigen expressed in the vast majority of human tumors and is presently one of the most promising target candidates for a therapeutic cancer vaccine. TRT is also expressed at low level in selected tissues and should be considered a self antigen. In the present study we sought to develop cytotoxic T lymphocytes (CTL) responses directed against human (h)TRT peptides with low relative affinity for which the available repertoire is to be preferentially spared from tolerance. This was accomplished by using analogue peptides of hTRT whose relative affinity for the MHC was increased by a targeted (-->Tyr) substitution in position one. By immunizing HLA A2.1 transgenic mice with these analogue peptides, we identified one such low relative affinity peptide (p572) that is endogenously processed and presented by HLA A2.1 in tumor cells, and is recognized by specific CTL. We used the highly immunogenic analogue peptide to successfully induce TRT-specific CTL in cancer patients and normal donors. CTL against p572-lysed human and mouse tumor cells but not activated autologous B cells. This peptide represents, therefore, an important candidate component of a cancer vaccine based on a TRT substrate and validates the strategy of targeting peptides with low affinity for the MHC for cancer immunotherapy.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	HLA-A2 Antigen Metabolism T-Lymphocytes, Cytotoxic Drug Effects Immunology Telomerase Pharmacology Amino Acid Motifs Amino Acid Sequence Amino Acid Substitution Animals Antigen Presentation B-Lymphocytes Binding Sites Cancer Vaccines Genetics Cross Reactions Cytotoxicity, Immunologic DNA-Binding Proteins HeLa Cells In Vitro Techniques Kinetics Mice Mice, Inbred C57BL Mice, Transgenic Peptide Fragments Prostatic Neoplasms Therapy Tumor Cells, Cultured Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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