Business Wire - November 15, 2004
The new data was published in the November 15 issue of the Journal of Immunology and authored by Dr. Rita Effros and colleagues at the Department of Pathology & Laboratory Medicine and the University of California, Los Angeles AIDS Institute, David Geffen School of Medicine, Los Angeles, California. The authors had previously found that telomere loss in cytotoxic T-lymphocytes (CTLs), the cells responsible for killing HIV-infected cells, was accelerated in AIDS patients, and contributed to the loss of anti-HIV activity that occurs during disease progression. Moreover, they showed that introduction of the telomerase gene into populations of HIV-restricted CTLs increased their lifespan, and, in a clonal population of CTLs, enhanced key anti-HIV cytolytic and viral suppression functions of these cells.
The present study examined HIV-specific CTLs from a broader range of donors. The new study confirmed CTL lifespan extension upon introduction of the telomerase gene, and demonstrated that bulk cultures (not clonally selected) of telomerase-transduced CTLs had enhanced HIV suppressing activity that persisted over a longer period of time compared to similar cultures of control cells. The telomerase-transduced CTLs had a prolonged capacity to produce anti-viral cytokines in response to HIV-specific stimulation. The authors also addressed how telomerase was achieving these beneficial effects by showing that telomerase transduction stabilized CTL telomeres (which otherwise continuously shortened) and significantly delayed the disease-related loss of a key T-cell signaling molecule, CD28. "Our results suggest that telomere shortening is a major driving force behind immune dysfunction observed in late stage HIV-1 disease," stated Dr. Rita Effros, senior author of the study. "And that telomerase activation, by prolonging protection by HIV-1-specific CD8+ CTLs, represents a promising strategy for HIV-1 therapy."
Geron Corporation provided UCLA the telomerase gene used in the study and has collaborated with Dr. Effros on studies of cellular dysfunction in the immune system of AIDS patients. "This work is part of our program evaluating the potential of telomerase activation for the treatment of chronic diseases," stated Calvin Harley, Ph.D., Geron's chief scientific officer. "We are excited by the results and are now working with Dr. Effros in testing our small molecule activators of telomerase as potential drug candidates for patients infected with HIV-1."
"These results confirm an important potential clinical application for our telomerase activator drug," said Thomas Okarma, Geron's president and chief executive officer. "Using gene transfer technology, we and others have published on the important role of telomere loss in specific cells critical for the pathogenesis of many chronic diseases as well as the potential therapeutic role of telomerase activation under these conditions. Our small molecule telomerase activator program is now positioned as an attractive therapeutic alternative to telomerase gene therapy in a growing list of chronic diseases, including HIV/AIDS."
Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for cancer based on its telomerase technology, and cell-based therapeutics using its human embryonic stem cell technology.
This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding future applications of Geron Corporation's technology constitute forward-looking statements involving risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, need for additional capital, reliance on collaborators, need for regulatory approvals or clearances, and the maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Geron's periodic reports, including the quarterly report on Form 10-Q for the quarter ended September 30, 2004.
CONTACT: Geron Corporation
David L. Greenwood, 650-473-7765
SOURCE: Geron Corporation
041115
BW041108
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