Introgen Therapeutics Inc announced the publication of data from preclinical studies demonstrating that the combination of its INGN 241 therapy and Genentech's Herceptin (trastuzumab) led to enhanced killing of HER-2/neu- overexpressing breast cancer cells in culture and in animal models of disease.
These data appear in the current issue of Surgery in a paper titled, "Combination therapy of Ad-mda7 and trastuzumab increases cell death in Her- 2/neu-overexpressing breast cancer cells." The study was performed in collaboration with Dr. Kelly K Hunt, associate professor of Surgical Oncology and chief of Breast Cancer Surgery at The University of Texas M D Anderson Cancer Centre.
MDA-7, the active component of INGN 241, is a multi-functional tumour suppressor gene. INGN 241 has been the subject of clinical studies in a variety of solid tumour types and is currently being tested in a Phase 2 clinical trial for melanoma.
"Therapeutic antibodies such as Herceptin have been shown to have very favourable safety and tolerability profiles compared with chemotherapy, and we believe that the combination of INGN 241 and antibody-based therapies may provide enhanced tumour cell killing with fewer side effects than chemotherapy or radiotherapy," said Sunil Chada, Introgen's director of research and development. "Therapeutic antibodies revolutionized cancer therapy, and we believe that gene-based therapies such as INGN 241 and our lead clinical candidate Advexin may have a similar impact on how cancer is treated," Chada added.
In the studies reported today, INGN 241 and Herceptin were evaluated alone or in combination in cancer cells that overexpress Her-2/neu as well as in cancer cells that had normal levels of Her-2/neu. Results of the studies demonstrated- INGN 241 inhibited the growth of breast cancer cells regardless of Her-2 status; Herceptin inhibited the growth only of cells that overexpress Her-2/neu. In Her-2-positive cells, low doses of Herceptin greatly enhanced the cell-killing activity of INGN 241.
The combination of INGN 241 and Herceptin significantly decreased the expression of several cancer-causing genes compared with controls and compared with either treatment alone.
For Her-2-positive breast tumors, the time to doubling of tumor volume was more than five times higher in mice treated with INGN 241 and Herceptin than in animals treated with saline (28 days and 5 days, respectively). In this assay, INGN 241 was a more effective monotherapy than Herceptin (21 days and 14 days, respectively).
Dr. Hunt said, "Combining multiple therapies to attack cancer on several fronts has been a key advancement in the treatment of cancer. The combination of INGN 241 and Herceptin is an example of how biologic therapies can be combined to provide potent cancer cell killing activity with favourable safety and tolerability profiles. In patients with cancer, high levels of HER-2/neu correlate with poor prognosis, increased tumour formation and metastasis, and resistance to chemotherapeutic agents. The ability of INGN 241 to enhance the activity of Herceptin in these aggressive tumours is very exciting. The results of these studies demonstrate the potential utility of INGN 241 as both a monotherapy or as part of combination regimens."