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Gene courier targets skin-tumor cells.

Researchers are reporting another first in the annals of gene therapy: the use of fat-like molecules to deliver DNA with cancer-killing potential into the tumors of people with skin cancer. These preliminary results take scientists one step closer to gene therapy for cancer, they contend.

Last October, genetic engineers used a crippled virus to deliver a therapeutic gene to the nasal cells of three people with the inherited illness cystic fibrosis (SN: 10/23/93, p.260). Some scientists still worry that such altered viruses may cause disease in humans.

Gary J. Nabel, a Howard Hughes Medical Institute researcher at the University of Michigan Medical Center in Ann Arbor, and his colleagues turned to liposomes, artificially produced fat particles that have long been used to ferry toxic chemotherapeutic drugs into human cells. Nabel and his colleagues now show that such molecules can also usher DNA into tumor cells in the human body.

"I think the results are fascinating;' comments molecular biologist Joseph Ilan of Case Western Reserve University School of Medicine in Cleveland, Ohio. Ilan's team is using liposomes to courier therapeutic genes to cancers in animals. Ilan, Nabel, and other scientists believe that liposomes may prove safer than viral vectors in the race to deliver therapeutic genes to human cells.

The Nabel team began its landmark experiment by mixing together liposomes and the DNA that makes up the HLA-B7 gene. They picked HLA-B7 because it is part of a class of genes that helps the immune system recognize foreign tissue. The researchers wanted to find out whether HLA-B7 could trigger an immune attack on malignant skin tumors.

They injected the liposome-DNA mixture directly into the cancerous skin tumors of five patients, none of whom had this type of HLA gene. The five volunteers suffered from malignant melanoma, a deadly form of skin cancer that kills some 6,800 people in the United States each year. The recruits had an advanced form of the disease that would not respond to conventional anticancer therapies.

in all five patients, the team found evidence that the HLA-B7 gene had turned on and was directing the production of its protein product. Since none of the recruits had inherited the HLA-B7 gene, any evidence of the protein had to come from the introduced gene, Nabel says.

In addition, the researchers demonstrated evidence of an immune response in two patients. Once the gene is deposited inside the tumor cell, the researchers believe, production of the "alien" protein acts as a red flag to the immune system. Nabel expects that the immune cells will then recognize those tumor cells as foreign and mount an attack.

Only a fraction of tumor cells take up the gene, a technical problem related to the gene-carrying capacity of the liposome, Nabel says. Yet the researchers believe that once immune cells travel to the tumor site, they may kick off a broadbased attack, one that eventually seeks out all malignant cells, not just ones carrying the HLA-B7 gene.

Although this study was not designed to prove the therapy's efficacy, one man showed a dramatic positive response, Nabel's team reports in the Dec. 1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. In that case, a skin tumor that had been injected directly with the experimental mixture completely disappeared, as did several other tumors that were not treated. Nabel thinks revved-up immune cells traveling through the man's bloodstream may have destroyed the uninjected tumors. This same man also had a tumor that did not respond to treatment.

The injections caused no toxic effects, the research group says. However, additional studies are needed to prove the therapy's safety and efficacy. "Five patients simply isn't enough;' points out gene therapy researcher R. Michael Blaese at the National Cancer Institute in Bethesda, Md.

This trial and others like it are important because they pave the way for more advanced studies of gene therapy's ability to fight cancer in humans, Blaese adds.
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Title Annotation:liposomes used to carry therapeutic genes
Author:Fackelmann, Kathy A.
Publication:Science News
Date:Dec 4, 1993
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