Ingenex Inc., a private biotechnology company in Menlo Park, Calif.,is beginning a pilot clinical study of its multidrug resistance (MDR)gene therapy to prevent toxic side effects associated with Taxol andenable patients to take twice as much of the cancer drug.The study will involve 10 patients with advanced ovarian cancer at theUniversity of Texas M.D. Anderson Cancer Center and will take fromnine to 12 months to complete."Patients with advanced ovarian cancer have a 6 percent to 7 percentresponse rate at current dosage levels of Taxol," said Ingenex Presidentand CEO Louis Bucalo. "At double the dosage we see a 65 percentresponse rate, but at that dosage patients experience a life-threateningeffect from the Taxol."Taxol is the brand name for paclitaxel and is marketed in the U.S. byBristol-Myers Squibb Co., of New York.Bucalo said Ingenex uses its MDR-1 gene to genetically modifypatients' blood precursor cells as a means of protecting bone marrowand blood cells from toxic effects of chemotherapy. Cells are altered exvivo and put back in the patients. Bucalo said that with each Taxoltreatment the modified cells should increase and allow patients toreceive stronger doses of the cancer drug.The MDR-1 gene protects blood cells by producing p-glycoprotein,which "pumps out" anti-cancer drugs from healthy cells before theycan be damaged.The pilot study will examine several factors: to make sure thegenetically modified cells continue to act like normal cells; to see if thealtered cells increase in number in the patients' blood; and to find out ifthe gene therapy prevents the decrease of white blood cells caused byTaxol treatments. The participants in the study will receive escalatingdoses of Taxol up to twice the levels currently used."We will be correlating the enrichment of modified cells with theprotection of the blood count post-Taxol administration," Bucalo said,"and assess whether there is a significant change in the level ofprotection."If the pilot trial results are favorable, Ingenex plans to conduct similarstudies with advanced breast and lung cancer patients.Bucalo said that in addition to targeting Taxol-related side effects,Ingenex intends to test its MDR gene therapy against toxicityassociated with other forms of chemotherapy. He added that Ingenexalso is involved in discussions with potential corporate partners.Ingenex, founded in 1992, is part of Titan Pharmaceuticals Inc., whichis a biopharmaceutical holding company based in South San Francisco.Other Titan companies are Geneic Sciences Inc., of Menlo Park, andTheracell Inc. and Ansan Inc., both of South San Francisco. n

-- Charles Craig

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