Telomerase Used as Cancer Vaccine - Brief Article

Applied Genetics News, April, 2000

Researchers from the UC San Diego School of Medicine and Cancer Center are investigating the use of telomerase as a universal cancer vaccine. Telomerase, an enzyme that maintains normal chromosome length during cell replication, is possibly the first gene to play a direct role in tumor transformation of cells by allowing precancerous cells to become immortal.

A team led by Maurizio Zanetti, M.D., UCSD professor of medicine, in collaboration with the Institut Pasteur in Paris, has used a prototype vaccine in cancer cells in vitro to activate a type of lymphocyte called cytotoxic T- lymphocytes (CTL), or killer cells, to destroy cancer cells using telomerase as a target. Their results are reported in the April 4 issue of the Proceedings of the National Academy of Science.

Zanetti theorized that by immunizing lymphocytes from cancer patients against telomerase, killer cells targeting telomerase would be generated. Because telomerase activity is elevated in cancer cells, telomerase peptides could then serve as a beacon for CTL, which would selectively destroy the cancer.

The team tested a prototype vaccine made from CTL-specific pieces of telomerase reverse transcriptase (hTRT) using blood cells from prostate cancer patients and, for comparative purposes, from healthy individuals. They observed that lymphocytes from prostate cancer patients were readily activated into CTL following immunization with the prototype vaccine, attacking and killing the cancer cells.

Because telomerase is over-expressed in the vast majority of all human cancers, they also tested the possibility that because of this over-expression, CTL produced against one type of cancer would recognize and destroy other types of cancer as well. They added CTL produced in the prostate cancer cell samples to other human cancer cells--breast, colon, lung, and melanoma--and found that the killer cells targeted the hTRT peptides in these cells as well and destroyed them.

Because telomerase is essential in the normal process of cell division, Zanetti and his team also looked for negative effects of this vaccine on normal human stem cells, which have a rapid reproduction rate and therefore higher levels of telomerase than normal cells. No adverse activity was detected. Since telomerase levels in normal cells is low, they believe there is little danger that this approach would cause an autoimmune reaction, with the body attacking its own normal cells. However, they acknowledge that this and other potential problems require further study.