Preclinical study shows that INGN 241 is even more effective against cisplatin-resistant ovarian and lung cancer cell lines than cisplatin-sensitive cell lines due to a metabolic defect in the drug-resistant cells, according to a presentation at the annual meeting of the American Association of Cancer Research.

The researchers were surprised to find that the anti-cancer activity of INGN 241 was more pronounced in cisplatin-resistant cells. Additional studies were then undertaken to determine the molecular basis for this observation. Data showed that cisplatin-resistant cells have a defect in a protein degradation pathway leading to accumulation of the active metabolite, MDA-7 protein, and resulting in enhanced apoptotic activity.

"Chemo-resistance poses a significant barrier to achieving good clinical outcomes, and leaves many cancer patients with limited treatment options," said Rajagopal Ramesh, MD, Associate Professor, Department of Thoracic and Cardiovascular Medicine at M. D. Anderson and principal investigator of the study. "The results of these studies support the evaluation of INGN 241 in patients with cisplatin-resistant cancers, and open the door to a new area of oncology research and drug development."

Previously, a Phase I trial of INGN 241 had shown clinical activity in patients with advanced melanoma. A Phase II trial in patients with metastatic melanoma and a Phase III trial for solid tumors in combination with radiation therapy are ongoing.

The mda-7 gene was discovered by the laboratory of Dr. Paul B. Fisher, professor of clinical pathology at Columbia University. Introgen holds an exclusive worldwide license for all gene therapy applications from the Corixa Corporation.