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1615 Poydras Street - Suite 1000
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 J. Michael Mathis
Louisiana State University Health Sciences
Center Areas of Research: Cancer Virotherapy In 2005, more that 200,000 women in the US were diagnosed with breast cancer. It is the most common malignant and the second leading cause of cancer death in women. Unfortunately, 30% of patients will present with advanced disease, and therefore, it is not uncommon to encounter patients who present with advanced disease. Recurrence remains a concern and effective therapy in such situation is marginal. Therefore, novel therapies are sorely needed. Dr. Mathis, Director of the Gene Therapy Program at
LSUHSC in Shreveport, is working on a project to engineer an adenovirus
with the ability to seek and destroy cancer cell while leaving healthy
tissues unscathed. Although attempted in the past, the idea of turning
viruses loose on cancer was abandoned because of toxicity and inefficacy.
However, this virotherapy approach has reemerged with great promise,
in large part due to better understanding of and the ability to genetically
modify viruses. The goal of this project is to develop an advanced
generation of virotherapy agent using the biology of breast cancer
to target this disease. To produce an adenovirus virotherapy agent
that targets breast cancer, a modification of a functional gene called
E1A within the adenovirus that is absolutely necessary for efficient
multiplication, such that it is only active in tumor cells but not
normal cells. A second modification was added such that the E1A protein
is only produced in tumor cells. Finally a third modification was
added such that the adenovirus is efficiently taken up by tumors
but not by liver where the majority of toxicity arises. Other projects involve using conditionally replicative adenoviruses (CRAds). CRAds are attenuated viruses, which have been designed to replicate within tumor tissues to achieve specific oncolysis. Along with Dr. DeBenedetti, Dr. Mathis has constructed a CRAd that is regulated at the level of protein translation to achieve tumor-specific oncolysis. In addition, Dr. Mathis has constructed an adenovirus-based vector to deliver the herpes simplex virus thymidine kinase (HSV-Tk) suicide gene that is regulated at the level of protein translation. These vectors are currently at the pre-clinical stage of animal experiments for the treatment of breast cancer, ovarian cancer, and head and neck cancer. Selected Publications: Mathis, J.M., Steward, P.L., Zhu, Z.B., and Curiel, D.T. Advanced generation adenoviral virotherapy agents embody enhanced potency based upon CAR-independent tropism. Clinical Cancer Research, (2006) May; 12(9): 2651-2656 Li, J., Le, L., Sibley, D.A., Mathis, J.M., and Curiel, D.T. Genetic incorporation of HSV-1 thymidine kinase into the adenovirus protein IX for functional display of the virion. Virology, (2005) August; 338(2): 247-258 Mathis, J.M., Stoff-Khalili, M.A., and Curiel, D.T. Oncolytic adenoviruses – selective targeting to tumor cells. Oncogene, (2005) November; 24(52): 7775-7791 Sasaki, M., Mathis, J.M., Jennings, M.H., Jordan, P., Wang, Y., Ando, T., Joh, T., and Alexander, J.S. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector. Journal of Inflammation, (2005) October; 2(1): 13 Stoff-Khalili, M.A., Rivera, A.A., Glasgow, J.N., Le, L.P., Stoff, A., Everts, M., Tsuruta, Y., Kawakami, Y., Bauerschmitz, G.J., Mathis, J.M., Pereboeva, L., Seigal, G.P., Dall, P., and Curiel, D.T. A human adenoviral vector with a chimeric fiber from canine adenovirus type 1 results in novel expanded tropism for cancer gene therapy. Gene Therapy, (2005) December; 12(23): 1696-1706 |
