GENE THERAPY: P53 Induces Cancer Destruction

Applied Genetics News,  Feb, 2001  

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Collaborators of Introgen Therapeutics, Inc. (301 Congress Ave., Suite 1850, Austin, TX 78701; Tel: 512/320-5010, Fax: 512/320- 4166) have published a preclinical study in the January 2001 issue of Clinical Cancer Research demonstrating that INGN 201 (Adenoviral-p53) can stimulate human immune cells to selectively kill cancer cells over-expressing the p53 gene. The p53 gene is over-expressed in approximately 50% of all human cancers. INGN 201 is a gene-based drug currently in Phase III clinical trials to treat patients with head and neck cancer by direct tumor injection, regardless of whether they over-express p53. The principal investigator of this study was Dmitry Gabrilovich, associate professor of oncology at the H. Lee Moffitt Cancer Center. Sunil Chada, director of research and development at Introgen, co-authored the publication.

The article demonstrates that dendritic cells treated with INGN 201 were able to induce a specific antitumor immune response mediated by cytotoxic T-lymphocytes, or killer T-cells. These killer T-cells recognized and killed tumor cells that over- expressed either mutant or normal p53, but not cells expressing normal levels of p53. An adenovirus without the p53 gene was not effective. A previous publication by these authors demonstrated that when such INGN 201 treated dendritic cells were administered to mice bearing cancers, p53 over-expressing tumors were killed. This study shows that the approach can be used with human tissue as well. In eight out of nine cancer patients, killer T- lymphocytes (T-cells) were generated which could recognize and kill cancer cells that over-expressed either mutant p53 or wild- type p53.

"This study suggests a new mechanism by which intratumoral injections of INGN 201 may be functioning," says James Merritt, vice president of clinical affairs at Introgen. "Furthermore, clinical adoption of this technique may in fact broaden the use of INGN 201 to treat widely dispersed metastatic tumor cells."

In a separate development, Introgen was awarded a $238,000 Small Business Innovation Research (SBIR) grant from the National Cancer Institute. The grant will fund collaborative research between Introgen and Stephen Swisher, assistant professor at The University of Texas M. D. Anderson Cancer Center, Department of Thoracic and Cardiovascular Surgery. Sunil Chada is the principle investigator for the grant. The research collaboration will help advance the preclinical development of INGN 241 (Adenoviral-mda7), a gene-based drug for the induction of apoptosis (programmed cell death) in various tumor types.

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