Preliminary tests with a new enzyme-based vaccine may provide a basis for the potential development of a "universal" cancer treatment.
"This vaccine is quite novel because tumor antigens are generally cancer-specific and have a specific set of determinants," said lead researcher, Dr. Eli Gilboa, director of the Center for Genetic and Cellular Therapies. "This study suggests that this may not be necessary and that a common antigen does exist."
The research, which was funded by an anonymous donation to the Duke Comprehensive Cancer Center, will be reported in the Sept. 1 issue of Nature Medicine and is currently the only paper in the United States describing human-tumor tests with this vaccine.
The telomerase-based vaccine slowed tumor growth in mice. For human tumors grown in test tubes, this vaccine stimulated the development of immune cells, which recognized and killed multiple cancer cells. No other vaccine induced such a wide immune response against both mouse and human cancer cells.
"The development of this vaccine is exciting because most vaccines now only work against a small population of cancers," said Dr. Johannes Vieweg, co-investigator and assistant professor of urology. Vieweg's lab confirmed Gilboa's results by providing the most compelling evidence that the vaccine worked against various human cancer cells grown in test tubes.
Telomerase, an enzyme expressed in 85 percent of cancers, reconstructs chromosomal ends in cancer cells, allowing them to multiply abnormally. Because it is so prevalent in cancers, it can feasibly be targeted as a universal antigen against the disease.
"Telomerase is an important component in prolific cells and is particularly overexpressed in cancer cells because of their rapid division," Gilboa said. "Our hypothesis was that the immune system could be trained to distinguish normal cells with tumor cells exhibiting telomerase overexpression."
The enzyme's combination with other universal antigens may provide a vaccine with even broader applicability. "This vaccine also reduces the complexity of developing vaccines since there is one universal antigen for all cancers," Gilboa said.
Gilboa and Vieweg are currently planning clinical trials involving the telomerase-based vaccine. Both are optimistic about its success. "None of the current standard treatments for metastatic cancer patients have convincingly shown to have an impact on survival and are also fairly toxic," Vieweg said. "This approach is easily targetable, has no harmful side effects and has shown great promise [in early studies]."
Further research will be done primarily with metastatic patients who have no other treatment options. The scientists must first establish a safe dose for these individuals and then monitor its efficacy in activating the immune system optimally. The researchers would also like to extend their observations to more cancers.
However, both Gilboa and Vieweg warn that a marketable panacea is still far off. "It's still a long way for us to demonstrate that this vaccine will be completely effective," Gilboa said. "We are and have to be cautious about our expectations."
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