Mesothelin Engineered On Virus-like Particles Provides Treatment Clues For Pancreatic Cancer

The protein called mesothelin appears to play an important role in promoting pancreatic cancer growth, said the senior author Dr. Qizhi (Cathy) Yao, professor of surgery -- vascular surgery at BCM. She, along with co-lead authors Dr. Min Li, assistant professor of surgery, and research associate Dr. Uddalak Bharadwaj carried out the studies of the protein that is found on the tumor cells' surface.

"Mesothelin is found in other cancers for several years," said Yao, also a researcher in the Dan L. Duncan Cancer Center at BCM. "However, we didn't know the role it played in pancreatic cancer:" until she and her colleagues reported in this article. In fact, they found very high levels of mesothelin in 18 of 21 samples of patient's pancreatic tissues compared to amounts found in nearby normal tissues. In studies of this protein in the lab, pancreatic cancer cell lines that produced high levels of mesothelin grew faster and spread more than those in which mesothelin levels were lower.

Pancreatic cancer cells grew and spread faster in mice whose tumors expressed high levels of mesothelin than in those whose cancer did not, said the researchers, who conducted the studies in an immune deficient mouse.

"We saw this molecule as very significant in the life of the tumor cells," Yao said. "Our next step is to identify whether this would be a good active immunotherapy target."

Making a treatment vaccine of virus-like particles (VLPs) that contained mesothelin, researchers injected mice having pancreatic cancer with this vaccine three times. Virus-like particles have the unique property of inducing protective immune responses but they lack the infectious capacities of the original virus.

Tumor growth in the immunized mice slowed and in some cases the tumor disappeared. The average life span for the mice not treated was four weeks. The immunized mice survived five weeks longer than those not treated.

Researchers found that the immunization works by suppressing production of key immune system cells that suppress the body's ability to fight the tumor. The researchers said pancreatic cancers produce these cells, called T regulatory cells, as a protective measure.

"If we are able to see the same results in humans, this would allow us to incorporate a combination therapy to treat the tumor," Yao said. "Treatment with a single drug is not effective."

Yao and her colleagues are seeking U.S. Food and Drug Administration approval to begin studies using their vaccination on people suffering from pancreatic cancer.

Other BCM researchers who took part in the study include Drs. Rongxin Zhang, Sheng Zhang, Hong Mu, William Fisher, F. Charles Brunicardi, and Changyi Chen. The article is available at http://mct.aacrjournals.org/.

Funding for the study came from grants from the National Institutes of Health, the Dan L. Duncan Cancer Center at BCM and the American Cancer Society.