Identification of immunogenic peptides of the self-tumor antigen: our experience with telomerase reverse...

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.