Telomerase immunity from bench to bedside: round one

Telomerase, a reverse transcriptase primarily devoted to the elongation of telomeres in mammalian cells, is also the first bona fide common tumor antigen. In fact, telomerase is over-expressed in > 85% of tumor cells irrespective of origin and histological type. In the past seven years, there has been considerable interest in assessing telomerase as substrate for vaccination in cancer patients to induce CD8 T cell responses. Because the activation of T cells is restricted by the MHC molecules on antigen presenting cells or tumor cells, the identification of telomerase peptides immunogenic for humans is tightly linked with HLA types. To date, a handful of peptides have been identified through a variety of screening procedures, including bioinformatics prediction, in vivo immunization of HLA transgenic mice, in vitro immunization of PBMC from normal donors and cancer patients, and processing in human tumor cells. Currently, there exist putative peptides for five major HLA types (A2, A1, A3, A24 and B7). Due to the complexity of the HLA system, trials have been performed focusing on the most prevalent HLA type, HLA-A2. Here, we summarize this collective effort and highlight results obtained in Phase 1 trials including a Phase 1 trial performed at the UCSD Cancer Center.