Identification of immunogenic peptides of the self-tumor antigen: our experience with telomerase reverse transcriptase.
The general approach, termed reverse immunology, to predict and identify immunogenic peptides from the sequence of a gene product of interest has been postulated to be a particularly efficient, high-throughput approach to discover tumor antigens. This laboratory has successfully identified immunogenic peptides of the human telomerase reverse transcriptase (hTERT), a self-tumor antigen, by using a multi-step approach. These steps include the following: the use of predictive bioinformatics algorithms, molecular methods to identify tumor-specific transcripts, prediction of proteasomal cleavage sites, peptide-binding prediction to HLA molecules and experimental validation, assessment of the in vitro and in vivo immunogenic potential of selected peptide antigens, isolation of specific cytolytic T lymphocyte clones, and final validation in functional assays of tumor cell recognition. This laboratory, and others have used similar methods to identify immunogenic peptides of self-tumor antigens, and many of those peptides are included in vaccines currently tested in clinical trials.
Cortez-Gonzalez
Xochitl
X
The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, CA, USA.
Zanetti
Maurizio
M
D000465:Algorithms; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D007114:Immunization; D051379:Mice; D008967:Molecular Biology / Q000379:methods*; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000378:metabolism*
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; D010455:Peptides; D019098:Telomerase