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Gene Therapy Success In The Laboratory Buoys Hope For Cancer Treatment And Prevention; Can Simply Swallowing A Gene Actually Treat And Prevent Cancer?

Date:
March 14, 2001
Source:
Thomas Jefferson University
Summary:
While the scientific jury is still out on that question, cancer geneticists and neuroscientists at Jefferson Medical College have seen stunning results in a gene therapy experiment in laboratory mice. The researchers have devised a technique to prevent and perhaps treat cancer by giving oral doses of gene therapy.

While the scientific jury is still out on that question, cancer geneticists and neuroscientists at Jefferson Medical College have seen stunning results in a gene therapy experiment in laboratory mice. Researchers, led by Carlo Croce, M.D., professor and chair of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and director of Jefferson's Kimmel Cancer Center, and Kay Huebner, Ph.D., professor of microbiology and immunology at Jefferson Medical College, have devised a technique to prevent and perhaps treat cancer by giving oral doses of gene therapy. The therapy greatly reduced the incidence of stomach cancer in animals already genetically prone to develop tumors and which had been exposed to a cancer-causing substance. While it's too early to say how effective this may be in humans, the work is another step in the development of safe and effective use of gene therapy for cancer.

"This is the first time we can prevent cancer by using gene therapy," says Dr. Croce. The technique could have potential use in several human conditions, such as in precancerous lesions in the lung, esophagus, head and neck, bladder and cervix.

Drs. Croce, Huebner, neuroscientist Matthew During, M.D., professor of neurosurgery at Jefferson Medical College and director of Jefferson's CNS Gene Therapy Center, and their co-workers report their results February 27 in the online version of the Proceedings of the National Academy of Sciences. The article will appear March 13 in the printed journal.

In the study, the researchers created genetically altered "knockout" mice lacking a gene called FHIT. Located in the human genome's most fragile region on chromosome 3, FHIT, when damaged, has already been implicated in contributing to a number of cancers, such as esophageal, stomach, kidney, breast and lung. Each mouse was exposed to nitrosomethylbenzylamine (NMBA), a carcinogen, beginning four weeks prior to therapy. The scientists' plan was to cause tumors to develop and then try to either prevent or slow their growth with gene therapy.

All of the 12 control mice receiving NMBA developed tumors. Each of eight mice in three therapy groups received one dose of gene therapy with a different type or combination of virus delivery systems. One group received the FHIT gene delivered through an adenovirus. Another group received an adeno-associated (AAV) virus-FHIT treatment, while the third received both viruses with the gene. In the third group, two mice died some time after treatment from pneumonia.

The results clearly showed a difference in the number of tumors. Every control mouse developed several tumors in the stomach. In the adeno-FHIT group, 50 percent had tumors. In the AAV mice, only three of eight had tumors.

"We were pretty surprised that it worked so well," says Dr. Huebner. "We knew we could kill cancer cells in the laboratory, but we didn't know if the viruses would get eaten up by the stomach juices. We expected differences, but not so dramatic."

"These results are very exciting," Dr. During says. "This is one of the first studies to demonstrate a gene transfer that is prophylactic. On the heels of the recent announcement of the sequencing of the human genome and our growing ability in genetic profiling, it's a step toward enabling us to treat high-risk individuals and reduce the likelihood of cancer."

In the histological exam, all of the control mice stomach sections were affected. In the AAV treated mice, 56 percent of the forestomach sections appeared normal, "another indication at the microscopic level of the dramatic effect," she says. They believe the AAV might result in longer expression of the FHIT gene.

The scientists think the technique may be a novel early stage approach to prevent and perhaps treat cancer.

The scientists say many hurdles still remain to effective and widespread use of gene therapy for cancer, not the least of which is getting the virus into every cell affected. Many regard gene therapy not so much a potential cure but rather part of the armamentarium of treatments aimed at controlling cancer.

"It will need a lot more study," Dr. Huebner says, adding that scientists would have to develop different techniques to deliver genes to other areas of the body, such as the lung, kidney and liver. One next step, she says, is to develop other animal tumor models. They are working to develop FHIT gene knockout models for both cervical and lung cancer. "We need to determine at what point the intervention would still work," she points out. "How early can we give the treatment and would it eliminate more of the tumors? If we started the treatment later in the tumor development process, would it still be effective? And how effective?"


Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.


Cite This Page:

Thomas Jefferson University. "Gene Therapy Success In The Laboratory Buoys Hope For Cancer Treatment And Prevention; Can Simply Swallowing A Gene Actually Treat And Prevent Cancer?." ScienceDaily. ScienceDaily, 14 March 2001. <www.sciencedaily.com/releases/2001/03/010301071728.htm>.
Thomas Jefferson University. (2001, March 14). Gene Therapy Success In The Laboratory Buoys Hope For Cancer Treatment And Prevention; Can Simply Swallowing A Gene Actually Treat And Prevent Cancer?. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2001/03/010301071728.htm
Thomas Jefferson University. "Gene Therapy Success In The Laboratory Buoys Hope For Cancer Treatment And Prevention; Can Simply Swallowing A Gene Actually Treat And Prevent Cancer?." ScienceDaily. www.sciencedaily.com/releases/2001/03/010301071728.htm (accessed August 28, 2014).

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