Cytotoxic T cell immunity against telomerase reverse transcriptase in humans

Telomerase is a ribonucleoprotein enzyme which has been linked to malignant transformation in human cells. Telomerase activity is increased in the vas t majority of human tumors, making its gene product the first molecule comm on to all human tumors. The generation of endogenously processed telomerase peptides bound to Class I MHC molecules could therefore target cytotoxic T lymphocytes (CTL) to tumors of different origins. This could advance vacci ne therapy against cancer provided that precursor CTL recognizing telomeras e peptides in normal adults and cancer patients can be expanded through imm unization. We demonstrate here that the majority of normal individuals and patients with prostate cancer immunized in vitro against two HLA-A2.1 restr icted peptides from telomerase reverse transcriptase (hTRT) develop hTRT-sp ecific CTL This suggests the existence of precursor CTL for hTRT in the rep ertoire of normal individuals and in cancer patients. Most importantly, the CTL of cancer patients specifically lysed a variety of HLA-A2(+) cancer ce ll lines, demonstrating immunological recognition of endogenously processed hTRT peptides, Moreover, in vivo immunization of HLA-A2.1 transgenic mice generated a specific CTL response against both hTRT peptides, Based on the induction of CTL responses in vitro and in vivo, and the susceptibility to lysis of tumor cells of various origins by hTRT CTL we suggest that hTRT co uld serve as a universal cancer vaccine for humans.