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Poster Presentation: Sun, Ma, Gao, Alsaggar, Hamhoom and Liu

Poster presentation: Assessment of IL-15/sIL-15Rα gene therapy on Lewis Lung Carcinoma growing in mouse lung, liver and kidneys.

Hao Sun, Yongjie Ma, Mingming Gao, Mohammad Alsaggar, Yahya Al Hamhoom and Dexi Liu
Department of Pharmaceutical and Biomedical Sciences, UGA College of Pharmacy

Story by Erin Geoffroy

Most cancer patients are killed not by their original tumor, but by metastases caused by malignant cells that migrate to other organs and thrive. In fact, this is true for nearly 90 percent of cancer deaths, according to the National Institutes of Health.

Surgical removal is often an option for primary tumors, although adjunct therapy is also used. But once cancer has spread, most patients are bombarded with radiation, chemotherapy or a combination of the two that causes harsh side effects.

Finding alternate therapies with fewer adverse effects is a high priority for cancer researchers. Among these seekers is fourth-year doctoral student Hao Sun, who works in the laboratory led by Dexi Liu, head of the department of pharmaceutical and biomedical sciences at the University of Georgia.

The Liu lab uses mouse models to search for genes encoding proteins that contribute to human diseases, and Sun’s focus is late-stage cancer. For the past several years, Sun’s experiments have concentrated on a potential drug treatment using the interleukin 15 (IL-15) gene. This gene makes interleukin 15 (IL-15), a chemical messenger that stimulates the body’s defenses.

“Its basic biological function of IL15 is to boost the immune system against tumor cells,” said Sun.

In typical lab experiments, scientists induce single, localized tumors by injecting malignant cells under the skin. Sun was able to produce simultaneous tumor growth in mouse lung, liver and kidneys with a high-speed, high-volume injection of cancer cells into the tail vein.

Three days after the tumor cell injection, Sun transferred the IL-15 gene via hydrodynamic delivery into the mouse’s liver. This produced IL-15, which was then secreted into the blood. The IL-15 protein circulated through the body, boosting the animal’s immune cells, such as killer T cells and NK (natural killer) cells.

Sun found that mice treated with IL-15 lived an average of 17 days after the tumor cell injection; untreated mice in the control group, in comparison, survived for only 10 days on average.

He treated a third group of cancer-ridden mice with Gemcitabine, a drug commonly used in cancer chemotherapy. The average survival time for these animals was 17.5 days, essentially the same as the IL-15 treatment group. A fourth group that received both IL-15 and gemcitabine lived an average of 33 days, the best outcome so far.

“If we combine the IL-15 gene therapy and the gemcitabine chemotherapy, we can prolong the survival time from 17 days to 33 days,” said Sun. “That’s huge.”

Because Sun used such an aggressive tumor model, survival time is short in these experiments. But he says this is not unlike what happens in people with late-stage cancer.

“For the late-stage tumor growth, it’s already very hard to treat,” said Sun.

Sun’s research is in the early pre-clinical stage, but he is encouraged by an apparent absence of side effects. . His goal is to demonstrate the effectiveness of IL-15 in treating tumor metastases and move to a clinical trial.

“With IL-15, the safety is better and it more effectively inhibits the tumor cells,” said Sun. “You’re boosting the immune system.”

This is hardly the first time that immunotherapy has been investigated as a cancer treatment, and it’s not the first attempt to use interleukins. Immunotherapy was thought to be a revolutionary treatment for late stage cancer in the 1970s, but it hasn’t lived up to those expectations. Progress has been slow and more research is needed.

Sun presented his research at the 2015 UGA Conference on Drug. He will graduate in May and hopes to work in an industrial setting where he can help expand treatment options for cancer patients.

This work has been published in Cancer Gene Therapy: http://www.ncbi.nlm.nih.gov/pubmed/26742578

Erin Geoffroy is a second-year graduate student in public relations at Grady College of Journalism and Mass Communication, UGA, and a reporter for Graduate Newsroom.