Cancer Programs : Telomerase Cancer Vaccine (TVAX)
The goal of therapeutic cancer vaccines is to ?teach? the patient?s own immune system to attack cancer cells while sparing other cells. This is done by exposing the immune system to a substance (an antigen) that is as specific to cancer cells as possible, thus inducing an immune response to any cells that present that antigen. We believe that telomerase?s characteristics make it an ideal antigen for cancer vaccines.
We are conducting basic and clinical research to confirm the safety and efficacy of telomerase vaccine therapies. In collaboration with scientists at Duke University, we published studies in the September 2000 issue of Nature Medicine, which demonstrate that cancer patients? immune cells can be activated with a telomerase vaccine in the laboratory to kill their own cancer cells. This technique was also effective in reducing tumors in animals. A Phase I/II study in prostate cancer patients at Duke University Medical Center is currently underway using this approach.
The Duke Phase I/II clinical trial uses an ex vivo (outside the body) process. Dendritic cells (the most efficient antigen-presenting cells) are isolated from the patient?s blood, pulsed with telomerase RNA, and then returned to the patient?s body where they instruct cytotoxic T-cells to kill tumor cells that express telomerase. This clinical trial is designed to enroll up to a total of 24 patients with metastatic prostate cancer, 12 of whom receive three weekly vaccinations (low-dose group), and 12 of whom receive six weekly vaccinations (high-dose group). As of June 1, 2004, the Duke researchers had treated and analyzed results for twenty patients. Over the next year, we plan to fund several optimization studies at Duke in order to enhance the current clinical protocols.
None of the patients have shown treatment-related adverse effects to date. All of the patients in the low-dose group showed a significant cellular immune response specific to telomerase. Levels of circulating cancer cells were reduced to normal in six of the eight patients who had significantly elevated levels of cancer cells circulating in their blood before the trial; and for a period of three months after treatment, PSA levels stabilized or declined in all three of the patients who had rising levels of PSA when they entered the study.
Seven of the eight patients in the high-dose group responded to the vaccine by generating telomerase specific cytotoxic T-cells. Patients in the high-dose group responded with a dramatic telomerase-specific T-cell response that increased over the treatment course and peaked 2 to 4 weeks after the final dose. Peak levels of their telomerase-specific T-cells were remarkably high, ranging from 0.9% to 1.8% of the total circulating cytotoxic T-cell pool. Telomerase-specific T-cells were detected for at least 16 weeks after vaccination.
Although the trial is designed primarily as a safety study, it was observed that patients in the high-dose group experienced a statistically significant increase in their PSA doubling time during the post-vaccination period when telomerase-specific T-cells were present. PSA doubling time (the rate of increase in PSA levels, expressed as the time it would take for a patient?s PSA levels to double) is a clinically used surrogate marker of disease progression. The median PSA doubling time in the high-dose group before vaccination was 2.9 months. After vaccination, the median PSA doubling time improved to 100 months. Moreover, of the 10 patients in the trial who were found to have elevated levels of circulating prostate cancer cells at the onset of the study, nine exhibited substantial reduction or complete clearance of their circulating tumor cells during the period in which telomerase specific T-cells were detected in the blood.
We own the rights to the telomerase antigen and its use in therapeutic vaccines. We also have a co-exclusive license from Merix Bioscience, which holds the rights for the ex vivo dendritic cell processing technology used in the Duke clinical trial. Under that license, we can use the technology with any defined antigen, including telomerase, to treat cancer.
In addition to our own development, we have granted a non-exclusive license to Dendreon Corporation to develop an ex vivo telomerase vaccine using Dendreon?s antigen-presenting system. In addition, we are pursuing the development of in vivo telomerase cancer vaccines. Geron scientists have demonstrated that direct, in vivo vaccination in tumor-bearing mice elicits a telomerase-specific immune response and causes reduced growth of the animals? tumors. Direct vaccination would eliminate the need for manipulation of dendritic cells in culture and potentially allow straightforward vaccination procedures to be available for all cancer patients in any oncology clinic.
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