Gene therapy holds great promise as it allows for a mechanism of altering gene expression in a tumor, and has potential to result in therapeutic gain. A regulated mechanism for gene expression is especially desirable for cancer gene therapy as this could maximize tumor cell killing while minimizing toxicity. Dr. Chuan Li of Duke University Medical Center has been working on a way to enhance gene expression using heat to activate the heat shock promoter, which subsequently initiates a "downstream" gene product.

We are studying the ability of heat to initiate intratumoral production of interleukin 12 (IL-12), a very powerful modulator of the immune system. The approach that we are taking should limit IL-12 expression to the tumor, with low levels of systemic exposure since the virus will be injected directly into the tumor and hyperthermia will be applied to the tumor. Even if some virus escapes into the circulation and infects normal tissues we would not expect gene expression outside the heated area.

We have preliminary data from the laboratory indicating that the combination of hyperthermia and IL-12 gene therapy leads to potent antitumor effects, particularly when this treatment follows radiation therapy.

At the College of Veterinary Medicine at North Carolina State University, we have begun testing heat-inducible gene therapy in cats with vaccine associated sarcomas. Many questions remain unanswered and only limited information is available to date. Work in this exciting area is supported by the National Cancer Institute and research funds are available to defray a significant portion of treatment costs in eligible patients.

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Donald E. Thrall, DVM, PhD

Professor of Radiology

N.C. State University

College of Veterinary Medicine

4700 Hillsborough St.

Raleigh, NC 27606

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