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.