Telomerase as a tumor-associated antigen for cancer immunotherapy.

ABSTRACT

Telomerase reverse transcriptase hTERT is an attractive target for cancer immunotherapy given its broad expression in human tumors and its demonstrated immunogenicity. Human and murine model systems demonstrate that CD8(+) cytotoxic T-lymphocytes (CTL) and CD4(+) helper T-lymphocytes can recognize dominant epitopes derived from TERT. CTL kill TERT-positive tumor cells of multiple histologies, although there is some disagreement regarding the level of processing and presentation of certain TERT peptides within the context of MHC class I molecules. CTL recognizing modified, low-affinity cryptic TERT epitopes have also been generated that protect against tumor challenge in a murine model. Several phase I clinical trials testing hTERT as a cancer vaccine target have shown the induction of T-cell immune responses but minimal toxicities, including bone marrow toxicity, in patients with multiple types of cancer. Several studies report some patients experiencing clinical benefit, including partial tumor regression, providing further encouragement for hTERT as broadly applicable target for cancer immunotherapy.