If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  First Adenoviral-p53 Gene Therapy Trial Shows Success In Lung Cancer DENVER, May 20, 1997 -- Researchers from The University of Texas M.D. Anderson Cancer Center reported that the first Adenoviral-p53 (Ad-p53) gene therapy study utilizing the tumor suppressor p53 gene was well-tolerated and showed evidence of clinical activity in patients with non-small-cell lung cancer, according to data presented here today at the 33rd Annual Meeting of the American Society of Clinical Oncology (ASCO). Additionally, the treatment appeared to be more active when used in combination with a common chemotherapeutic agent, cisplatin. "The results of this Phase I trial are preliminary but encouraging," said Dr. Jack A. Roth, Chairman of the Department of Thoracic and Cardiovascular Surgery at M.D. Anderson Cancer Center. "The treatment appears safe and did not cause any serious side effects. The p53 treatment also resulted in tumor regression in patients who had failed conventional treatments for their recurrent tumors. Based on these results, Introgen and RPR Gencell plan to initiate larger clinical trials in the United States in 1997." Clinical Results The Phase I trial, conducted at The University of Texas M.D. Anderson Cancer Center, was designed to study the safety of increasing doses of in vivo (inside the body) gene therapy in patients with lung cancer. Twenty-one patients were enrolled, all with advanced non-small-cell lung cancer that had not responded to conventional treatments. The study was a dose escalation trial; each of the 21 patients received the p53 treatment once a month (given via an adenovirus delivery system (vector) directly into a single primary or metastatic tumor); nine also received cisplatin intravenously over two hours, given three days prior to being injected with p53 gene. Twenty of the 21 patients could be evaluated for response. At higher doses, treated tumors in five of six patients stopped growing for varying periods of time and the sixth patient had a partial response that lasted over six months. The Ad-p53 construct was not effective at low doses. In eight of the nine patients who received both p53 and cisplatin, the tumor stopped growing for varying periods of time up to sixth months and one patient exhibited partial regression, defined as at least a 50 percent reduction in injected tumor. Tumor stabilization and regression were noted even in patients whose tumors had grown while previously receiving cisplatin chemotherapy. No adverse side effects attributable to the p53 gene were observed in any of the patients enrolled in the study. Role of p53 Over 50 percent of all cancers have a mutation of the p53 gene. p53 is a tumor suppressor gene that encodes a protein which responds to damage involving a cell's DNA. The protein activates one of two pathways in the damaged cell: a) a growth-arrest pathway in which cell division is halted until the DNA damage has been repaired or b) a cell-suicide or apoptotic pathway, in which heavily damaged cells undergo programmed cell death. Each of these pathways prevents mutations from being passed on to daughter cells and are important brakes in the development of certain cancers. These protective pathways become non-functional when as cell's own p53 genes are lost or mutated. Data produced in this clinical study suggest that adenoviral-p53 therapy may also benefit cancer patients bearing tumors without p53 mutations. Introgen Therapeutics and RPR Gencell Introgen Therapeutics, Inc. an Austin-based company engaged in the development of cancer therapeutics, sponsors Dr. Roth along with 25 other clinicians and researchers at M.D. Anderson Cancer Center. Introgen and RPR Gencell, the gene therapy division of Rhone-Poulenc Rorer, are collaborating to develop and commercialize gene therapy products based on the p53 pathway and k-ras oncogene inhibition. Introgen Therapeutics, Inc. a leader in the development of gene-based cancer therapeutics, is a privately held company formed to commercialize anti-cancer technology developed at the University of Texas M.D. Anderson Cancer Center in Houston, Texas. Introgen's primary focus is the development of in vivo gene therapy products for a variety of cancers and development of vectors used to deliver genetic material constructs. RPR Gencell is the division of Rhone-Poulenc Rorer dedicated to the discovery, development, manufacture and commercialization of gene therapy products.
|
