An Entirely New Approach to Cancer Treatment
Oct. 26, 2000 -- By combining two cutting-edge technologies -- tissue engineering and gene therapy -- researchers have created a novel approach for treating ovarian cancer. Although it's still in preliminary testing, the nonchemotherapy, nonsurgery treatment is showing great promise in animals, say the Harvard researchers.
In order for gene therapy to work, cells that have been transfected -- or stuffed -- with therapeutic genes must be transplanted into the patient. But, there can be problems transplanting enough of them to make a difference, and often the cells die before they can produce their beneficial protein products, says lead author Antonia E. Stephen, MD, a research fellow at Harvard University and Massachusetts General Hospital in Boston. But in this newly developed system in which the transfected cells are supported on a synthetic polymer scaffold, "we can get an adequate number to survive and produce the protein of interest," she says.
The "protein of interest" for Stephen's team is müllerian inhibiting substance (MIS) -- the factor naturally produced by fetal and newborn human males to inhibit the development of female sex organs. In the lab, MIS had shown strong antitumor activity against certain ovarian cancers, but its availability is limited, and purifying enough of it is costly. Tissue engineering offered a way around those problems.
"We take animal cells and transfect them with the MIS gene," says Stephen. "We then seed those transfected cells onto a biodegradable polymer mesh and grow them in the laboratory for several days." The resulting 'engineered tissue graft' is then implanted into a mouse that also receives a human ovarian cancer tumor.
With the support of the polymer scaffolding, the transfected cells survive, and after about three days in the mice, they begin to produce MIS protein, the team reports. In 40 mice tested, levels of MIS in the blood were much higher than normal by 7-10 days, and they remained quite high for several weeks. Removing the scaffolding caused the MIS levels to drop back to normal.
When the researchers sacrificed the animals, they found that the mice carrying grafts made of MIS-transfected cells had significantly smaller tumors than did those animals given grafts of normal cells. "Tumors implanted into the animals have been inhibited with the production of the MIS," says Stephen.
The new approach looks good, but there's a long way to go before the work can move into humans. So far, Stephen tells WebMD, only "transformed, or essentially cancerous animal cells that grow on their own," have been transfected. "What we're working on right now is making an animal model with cells that do not grow on their own," she says. "That should be done soon."
The ultimate goal, she says, is transfecting a patient's own normal skin or muscle cells and then growing those cells on the scaffolding. "Where we stand now is that we have an animal model for this [new approach]," she says.
Stephen presented the findings this week at a medical conference in Chicago.