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INGN 241 enhances anti-tumour effects of Herceptin: Introgen

OrlandoSaturday, April 3, 2004, 08:00 Hrs  [IST]

Preclinical data presented at the 95th annual meeting of the American Association of Cancer Research (AACR) demonstrate that INGN 241 enhances the anti-tumour effects of Herceptin (Trastuzumab) in HER2-positive breast cancer. INGN 241, a novel product candidate designed to deliver the MDA-7/IL-24 gene to tumour cells, is being developed by Introgen Therapeutics, Inc. and is in Phase 1 and Phase 2 clinical trials in a variety of cancers. The data were generated in an ongoing collaboration between researchers at Introgen and The University of Texas M. D. Anderson Cancer Center. Dr. Sunil Chada, Introgen's director of research and development said, "These data demonstrate that enhanced cell killing of HER2-positive breast cancer cells can be achieved by combining INGN 241 with Herceptin. Tumour cells that overexpress HER2, a growth factor receptor that is the target of Herceptin, are more aggressive and difficult to treat than HER2-negative tumours. Herceptin has become an important treatment option for women with metastatic HER2-positive tumour's, and INGN 241 appears to enhance Herceptin's anti-tumour effects in a model of this aggressive form of cancer. These data demonstrate the potential for INGN 241 to improve the anti-tumour effects of approved cancer therapies." Abstract #5135, "Combination therapy of Ad-mda7 and Herceptin inhibits tumour growth in nude mice and increases apoptosis in HER2/NEU overexpressing breast cancer cells," described several molecular markers involved in cancer cell killing by INGN 241 and Herceptin as single agents or in combination. Although both agents caused significant tumour growth inhibition in an animal model of breast cancer, the combination of the two resulted in significantly enhanced growth inhibition. Results of this study demonstrate that the combination of Herceptin and INGN 241 produced a greater anti-tumour effect by decreasing levels of Akt and p-akt in HER-2/neu over-expressing breast cancer cells. The Akt and p-akt proteins are associated with cell growth, migration and metastasis. Abstract #4402, "Increased apoptosis in HER2/NEU over-expressing breast cancer cells by combination therapy of Ad-mda-7 and Herceptin," reported similar results from studies conducted in cultured tumour cells. Data from these studies show that INGN 241 and Herceptin each reduced viability and suppressed tumour growth of HER2-positive breast cancer cell lines when used as single agents. INGN 241, but not Herceptin, demonstrated a similar growth inhibitory effect in HER2-negative cells. In HER2-positive cells, INGN 241 significantly enhanced the anti-tumour activity of Herceptin, resulting in increased growth inhibition of cultured tumour cells.

 
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