Introgen Therapeutics Inc has published the new pre-clinical data from studies evaluating INGN 241 in combination with radiation therapy in an animal model non-small cell lung cancer (NSCLC), a company release said.
INGN 241 currently is in phase 2 clinical trials in malignant melanoma and has completed phase 1 - 2 studies in multiple solid tumour indications. The paper, titled "Adenovirus- Mediated mda-7 (IL-24) Gene Therapy Suppresses Angiogenesis and Sensitizes NSCLC Xenograft Tumours to Radiation," reports data from studies conducted by researchers at The University of Texas M.D. Anderson Cancer Center in collaboration with Introgen scientists and is available in the current version of Molecular Therapy.
The studies were conducted in the laboratory of Dr. Raymond E Meyn, professor and chairman of the Department of Experimental Radiation Oncology at The University of Texas M. D. Anderson Cancer Center, and evaluated the combination of INGN 241 and radiation treatment in mice implanted with human NSCLC tumours. Results demonstrated a substantial and prolonged inhibition of tumor growth following the combined treatment. Analysis of tumours revealed a significant reduction in two proteins (bFGF and VEGF) that regulate the formation of new blood vessels essential for tumour growth as well as a reduction in the number of small blood vessels and an increase in apoptosis in tumours treated with the combination regimen compared with either INGN 241 or radiation alone. Additional data show that MDA-7 protein sensitizes the cells that give rise to new blood vessels to the effects of radiation without affecting other normal cells.
"These data provide the first molecular basis for the inhibition of tumour growth by INGN 241 in combination in radiotherapy," said Sunil Chada, Introgen's director of Research and Development. "The formation of new vessels, a process known as angiogenesis, is essential for tumour growth. In the absence of angiogenesis, cells within the tumour are starved of oxygen and nutrients and die. The importance of angiogenesis in tumour growth has been validated by the recent approval of the first anti-angiogenic cancer therapy. In addition to its anti-angiogenic activity, a substantial body of data demonstrates that the MDA-7 protein has multiple anti-cancer effects, including inducing cell death, stimulating the immune system, reducing cell migration and metastasis and sensitizing cells to the effects of chemotherapy or radiation. Based on these activities, we believe that INGN 241 has enormous potential in treating a variety of cancers," he explained.
"In addition to being able to cure some animals with human lung tumours, we found a greater than 300 per cent increase in survival after treatment with INGN 241 and radiation combination therapy," said Dr Meyn. "This treatment regimen kills tumor cells directly and then kills the vasculature feeding tumours without evidence of toxicity. We evaluated the critical molecules involved in angiogenesis and demonstrated that the combination of INGN 241 and radiotherapy significantly suppressed their activity. This data provides an impetus to evaluate INGN 241 in combination with radiotherapy in patients with lung cancer," he added.
Introgen has funded sponsored research for Dr. Meyn. The Board of Regents of The University of Texas System owns stock in Introgen. These arrangements are managed in accordance with its conflict of interest policies, says the release.
Introgen is a leading developer of biopharmaceutical products designed to induce therapeutic protein expression using non-integrating gene agents for the treatment of cancer and other diseases. Introgen maintains integrated research, development, manufacturing, clinical and regulatory departments and operates a commercial-scale, CGMP manufacturing facility.