Potent anti-angiogenic effect for Introgen cancer drug
Introgen Therapeutics, from Austin, TX, has published new preclinical data from studies evaluating INGN 241 in combination with radiation therapy in an animal model non-small cell lung cancer (NSCLC). INGN 241 currently is in Phase II clinical trials in malignant melanoma and has completed Phase I - II studies in multiple solid tumor indications.
Introgen Therapeutics, from Austin, TX, has published new preclinical data from studies evaluating INGN 241 in combination with radiation therapy in an animal model non-small cell lung cancer (NSCLC). INGN 241 currently is in Phase II clinical trials in malignant melanoma and has completed Phase I - II studies in multiple solid tumor indications.
'These data provide the first molecular basis for the inhibition of tumour growth by INGN 241 in combination in radiotherapy,' said Dr 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 sensitising 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.'
The studies were conducted in the laboratory of Dr. Raymond 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 tumour 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 sensitises the cells that give rise to new blood vessels to the effects of radiation without affecting other normal cells.
'In addition to being able to cure some animals with human lung tumours, we found a greater than 300% increase in survival after treatment with INGN 241 and radiation combination therapy,' said Dr Meyn. 'This treatment regimen kills tumour 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.'
About INGN 241
INGN 241 is a modified adenoviral vector that carries the cancer cell killing mda-7 gene. The mda-7 gene encodes the antitumor cytokine, interleukin 24 (IL-24), the protein responsible for INGN241's broad therapeutic properties. Previous studies carried out have shown that the introduction of the mda-7 gene into cancer cells induces programmed cell death and also effects, likely through its cytokine properties, antitumor action in cancer cells far removed from site of administration.