LSU vet school professor uses gene therapy to destroy cancerous tumors

July 16, 2004

Shulin Li, associate professor in the LSU School of Veterinary Medicine's Department of Comparative Biomedical Sciences, is developing a gene therapy treatment for cancer that could ultimately serve to "vaccinate" bodies against tumor recurrence.

Thus far, Li's treatment has succeeded in pre-clinical trials on tumors in mice. Now he is using his method to treat larger animals, such as dogs, before seeking approval for human trials.

Li's research focuses on electroporation and cytokine gene therapy in cancer treatment. Electroporation involves injecting a therapeutic gene, or "tumor killer" gene, directly into the tumor. Then, an electric pulse is applied for less than one second. This process is repeated two to three times until the tumor is eradicated. Cytokine treatment, the next step in the therapy, involves the induction of "immuno-memory" into the patient. This allows the body to "remember" the particular type of cancer that it had and effectively vaccinates the patient against it.

"The treatment kills the tumor and helps the body develop a long-term, anti-tumor memory, which means that it becomes resistant to the tumor," explained Li.

Thus far, Li - who is collaborating with Dr. G. Neal Mauldin, director of the Vet School's Cancer Treatment Unit - has treated one dog, who was suffering from several cancerous tumors in and around its mouth. Li said that the dog was in very bad shape, but the treatment was largely a success. The dog's two smaller tumors were eliminated by the treatment, and about one third of the larger, more advanced tumor was eliminated. Unfortunately, the large tumor's size and location was inhibiting the dog's ability to eat and drink and the owner decided to have it put to sleep.

Li's work has been supported by grants from the National Institutes of Health. In order to continue treating larger animals, Li is now seeking additional funding from the NIH and the American Cancer Society.

"The grant will support the dog study, and then we can move on to human studies," said Li.

The dog study is limited by the type of cancer that the animal must have and the owner must give his or her consent. Nevertheless, Li, who came to LSU more than a year ago after research stints at the M.D. Anderson Cancer Center in Houston and the University of Arkansas Medical Center, said that the opportunity to apply the treatments to larger animals is one of the reasons he was attracted to the Vet School. Trying the treatment method on larger animals suffering from tumors allows for optimizing techniques and smooths the translation to human treatment, he said.

Li said that one of his existing NIH grants supports his work on the treatment that involves injections directly into the tumor, while another supports research into a method in which muscle is injected. The goal of the muscle-injection method is to attack smaller tumors and prevent their recurrence.

In addition to these methods, Li is researching a form of electrochemogene therapy. While younger, stronger immune systems may benefit from the electroporation immunogene therapy by itself, older, weaker immune systems may still require some traditional chemotherapy methods. This was the method that Li and Mauldin used to treat their first dog patient.

Li has had several articles published on his work in professional journals. His discovery of IL-12 (interleukin-12)-mediated, tumor-targeted genes was recently published in the journal Molecular Therapy, and the significance of his work was reported on the NIH's National Institute of Dental and Craniofacial Research Web site,

His recent paper titled "New Development of Electroporation Gene Therapy in vitro and in vivo" has been accepted by Current Gene Therapy, a journal that serves as an expert forum to convey current research on gene transfer and gene expression for analysis, animal models, vector development and human clinical applications for treatment of disease.

Louisiana State University

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