LSU School of Veterinary Medicine Conducts Cancer Research with Potential Human Applications
A dog’s tumor is treated using a combination
of chemo- and cytokine gene therapies. The tumor is greatly reduced after
seven weeks and is completely gone after 23 weeks.
When you think of a veterinary school, you usually do not think about human medicine. However, veterinary schools contribute a great deal to the study of human medicine and disease.
The LSU School of Veterinary Medicine has researchers that are working on such diseases as brain tumors, herpes viruses, cardiovascular disease, Lyme disease, cystic fibrosis, and cancer. Dr. Shulin Li, an associate professor in the Department of Comparative Biomedical Sciences at the LSU School of Veterinary Medicine, is conducting research on a combination of chemo- and cytokine gene therapies that could reduce cancerous tumors and make patients immune to a tumor recurrence. The treatment has been successful in pre-clinical trials with mice and ultimately can be used to treat cancer in humans.
Li’s research focuses on cytokine gene therapy via electroporation in the treatment of cancer. Electroporation involves the use of an electrical pulse to deliver a gene into the body for the treatment of cancer. Interleukin-12, a therapeutic gene, is injected directly into the tumor or other targeted tissues, and then an electrical pulse is applied for less than one second. Cytokine gene therapy involves inducing an immuno-memory into a cancer patient. This allows the body to remember the particular type of cancer that it had and effectively vaccinates the patient against it.
“Bleomycin electrochemotherapy has been successful in preclinical studies and clinical trials for treating squamous cell carcinoma and adenocarcinomy; however it is not effective for treating recurrent tumors or metastatic tumors, or for preventing tumor redevelopment,” said Li, whose research now shows that co-administration of bleomycin (chemotherapy) and Interleukin-12 via electroporation eradicates squamous cell carcinoma in 100 percent of mice and prevents tumor redevelopment in 80 percent of mice. “The primary role of bleomycin is to inhibit the tumor vessel development,” said Li. “The primary role of Interleukin-12 is to increase the immune response that extends the survival of treated mice and inhibits tumor development. This combination modality has great potential to be translated in a clinical setting for high-grade malignancies and for preventing tumor redevelopment.”
Interleukin-12 is the primary gene used in Li’s cytokine gene therapy. “Interleukin-12 has mechanisms that stimulate T-cell response and inhibit angiogenesis,” said Li. Because of this capability, it is theorized that Interleukin-12 can be used to treat many different types of cancers. Coadministration of Interleukin-12 and bleomycin induces a complete regression of high-grade breast tumors and inhibits metastatic tumor development in 60percentof mice.
Electroporation cytokine gene therapy has potential human applications. It has already been successful in treating oral carcinoma and breast cancer in mice. “This therapy could theoretically be used to treat oral cancers, breast cancer, melanoma, and prostate cancer in humans,” said Li. “The technology is mature enough to treat humans if funding is available. I am grateful for the support that I receive from the Department of Comparative Biomedical Sciences and the School of Veterinary Medicine administration.”
Dr. Li’s research is currently being funded by grants from the National Institutes of Health’s National Institute of Dental and Craniofacial Research and National Cancer Institute.
Li’s research has involved pre-clinical trials on mice, but it has now advanced to the point where trials have begun on larger animals, such as dogs. Li, along with Dr. G. Neal Mauldin, director of the School’s Cancer Treatment Unit, has treated two dogs with cancer using bleomycin chemotherapy and cytokine gene therapy. “One of the dogs experienced 50-percent tumor regression but had to be euthanized for other reasons,” said Li. The second dog had an oral carcinoma, and the tumor was treated with radiation. Though the radiation therapy removed the tumor, it returned after one month. The dog was then treated using bleomycin chemotherapy and cytokine gene therapy, and the tumor was gone after 23 weeks. The tumor has not recurred, and the dog is doing fine.
The Cancer Treatment Unit at the LSU School of Veterinary Medicine sees about three or four tumor-bearing patients a week. Patients are treated with chemotherapy or radiation therapy, or a combination of both. The presence of the Cancer Treatment Unit potentially allows for the practical application of Li’s research. If large animal trials are successful, this research can some day be used to fight cancer in humans.
Contact Ginger
Guttner| LSU School of Veterinary Medicine
Photos courtesy Ginger Guttner
LSU Office
of Public Affairs
Spring 2006
