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GERN publishes results of telomerase vaccine in prostate cancer:

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Geron Announces Publication of Phase 1-2 Telomerase Vaccine Study Results in Patients With Metastatic Prostate Cancer

MENLO PARK, Calif.--(BUSINESS WIRE)--March 4, 2005--Geron Corporation (Nasdaq:GERN - News) announced today the publication of results of a completed Phase 1-2 clinical trial of its telomerase therapeutic vaccine administered to patients with metastatic prostate cancer at Duke University Medical Center. Senior author, Dr. Johannes Vieweg, and colleagues from Duke published the results in the Journal of Immunology, available today online at http://www.jimmunol.org/.

The results show that the vaccination protocol successfully generated telomerase-specific T-cell responses in 19 of 20 subjects. The vaccine was well tolerated with no major treatment-related toxicities. Peak immune responses to vaccination were remarkably high with 1% to 2% of circulating CD8+ T-cells demonstrating anti-telomerase specificity. Vaccination was associated with a significant increase in PSA doubling time and clearance of circulating tumor cells.

Characteristics of the Immune Response in the Low-Dose Group

Twelve subjects each received three weekly injections of the vaccine. Eleven responded with significant levels of telomerase-specific CD8+ T-cells and nine developed significant levels of telomerase-specific CD4+ T-cells. Subjects who were vaccinated with a modified vaccine containing a lysosomal targeting sequence responded with higher frequencies and magnitudes of CD4+ telomerase-specific T-cells than those vaccinated with the unmodified vaccine. The telomerase-specific cytotoxic T-lymphocytes (CTLs) isolated from the peripheral blood of vaccinated study subjects killed telomerase targets in vitro. CTLs from subjects vaccinated with the modified vaccine demonstrated greater killing activity against telomerase targets than CTLs from subjects treated with the unmodified vaccine, suggesting that the improved CD4+ response augments CTL activity.

Characteristics of the Immune Response in the High-Dose Group

Eight subjects were treated with six weekly injections of the vaccine to determine if the magnitude of the immune response seen after three weekly injections could be further enhanced. Six weekly vaccinations resulted in robust CD8+ T-cell responses that peaked two to four weeks after the sixth injection, reaching levels of 1% to 2% of circulating CD8+ T-cells exhibiting anti-telomerase specificity. This high frequency of antigen-specific T-cell responses is comparable to those seen after vaccination for infectious diseases that result in clearance of the infection. The CD8+ telomerase-specific T-cells generated in patients immunized with the modified vaccine exhibited characteristics consistent with the development of central T-cell memory, a finding with important implications for designing an optimized schedule for boosting injections to prolong the duration of the vaccine response.

Clinical Response to Vaccination

Five subjects in the high-dose group were available for follow-up PSA analysis for at least two months after therapy. The median pre-treatment PSA doubling time in the high-dose group was 2.9 months. After six vaccinations, the median PSA doubling time increased to 100 months, a statistically significant change (p = 0.04). No significant change in PSA doubling time was seen in seven evaluable patients from the low-dose group.

Eighteen subjects were evaluated for the presence of circulating PSA-expressing prostate cancer cells in their blood before and after therapy. A total of 10 patients exhibited significant levels of circulating prostate cancer cells before therapy (four from the modified vaccine group and six from the unmodified vaccine group). Four out of four and five out of six of these patients, respectively, exhibited reduction or clearance of circulating prostate cancer cells after vaccination.

Implications of the Data

These data show that telomerase vaccination was associated with a significant impact on PSA doubling time and a reduction or elimination of circulating tumor cells during the time that a measurable, telomerase-specific T-cell response was detectable in the patient's blood. The modified vaccine produced a central T-cell memory response which should enable recall responses to additional vaccinations. These observations suggest that continued vaccination (boosting) to maintain the telomerase-specific T-cell response may enhance clinical impact.

"These results are very exciting," said Dr. Vieweg. "The high levels of telomerase T-cell immunity generated in these advanced cancer patients is striking. The temporal association between immunity and surrogate clinical response suggests a potential clinical impact of the vaccine. We are currently optimizing the vaccination protocol to extend the durability of the immune response to telomerase."

"We are obviously pleased with these results," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "Generating high levels of telomerase-specific killer T-cells in advanced cancer patients without causing toxicity was the primary objective of this study. We look forward to the results of our current studies designed to augment the response to vaccination and hopefully, to provide further evidence of clinical impact."
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