Results of a new preclinical study evaluating the mechanisms by which mda-7/IL-24, the active component of Introgen's INGN 241, kills non-small cell lung cancer cells have been published in Molecular Therapy, the official journal of the American Society of Gene Therapy.
Data from these studies, which were conducted in collaboration with researchers at The University of Texas M. D. Anderson Cancer Center, Baylor College of Medicine and The University of Texas Medical Branch at Galveston, identify a novel intracellular pathway through which mda-7/IL-24 causes lung cancer cells to undergo apoptosis (programmed cell death). Additionally, these studies highlight the ability of mda-7/IL-24 to exert its anti-cancer effects through a variety of pathways, depending on the gene expression patterns of various types of cancer cells.
Dr. Sunil Chada, Ph.D., Introgen's director of research and development, said, "These data identify a unique intracellular signal by which INGN 241 kills cancer cells. Expression of MDA-7 protein inside a cancer cell by treatment with INGN 241 activates a stress response pathway that results in selective apoptosis in cancer cells. These studies demonstrate that INGN 241 can work through multiple pathways to kill cancer cells, without exhibiting toxicity to normal cells. Cancer cells can mutate to develop resistance to chemotherapy and radiation therapy -- MDA-7 is unusual in that it can attack cancer cells via multiple mechanisms and thus may be a good candidate for cancers resistant to conventional therapies. The multiple anti-cancer activities of INGN 241 suggest that this product candidate may have utility in treating a broad array of cancers."
In the published study, researchers evaluated the role of MDA-7 protein inside and outside tumor cells. The presence of MDA-7 protein in a specific part of the cancer cell involved in secretion activates a stress response that ultimately leads to cell death. This is a previously unknown mechanism for tumor cell killing. In the lung cancer cells tested, the killing was caused by intracellular MDA-7 since these cells lack MDA-7 receptors on their cell surface. Other tumor cells express specific receptors for MDA-7 on their cell surface and can be killed by both intracellular and extracellular mechanisms that are induced in cancer cells. This study underscores the tumor cell selectivity of the tumor killing mechanisms of INGN 241.
Dr. Robert E. Sobol, Introgen's senior vice president of medical and scientific affairs said, "Patients with lung cancer have limited treatment options. The identification of a novel pathway for selectively inducing cell death in lung cancer cells may enable us to develop innovative approaches to therapy. To date, our clinical trials of INGN 241 have shown us that the INGN 241 product candidate has favorable safety and tolerability profiles and have provided data to support continued clinical development in lung cancer and other cancer indications."
The mda-7 gene was discovered by the laboratory of Dr. Paul B. Fisher, professor of clinical pathology and the Michael and Stella Chernow Urological Cancer Research Scientist in the Departments of Neurological Surgery, Pathology and Urology at Columbia University. Introgen holds an exclusive worldwide license for all gene therapy applications from the Corixa Corporation.