Advertisement
 

Human Gene Therapy Tested on Cancer : Medicine: Doctors inject a man with cells from his own tumor that had been genetically engineered in an attempt to 'immunize' his body.

October 09, 1991|MARLENE CIMONS | TIMES STAFF WRITER

WASHINGTON — Researchers at the National Institutes of Health on Tuesday performed the first experiment using human gene therapy to create a "cancer vaccine" that they hope will "immunize" patients against their own tumors.

Dr. Steven A. Rosenberg, chief of surgery at the National Cancer Institute, injected a 46-year-old man suffering from advanced melanoma--a lethal skin cancer--with cells from his own tumor that had been genetically engineered in the laboratory with the gene for the production of tumor necrosis factor. Tumor necrosis factor is a potent anti-cancer toxin which is naturally produced in small amounts by the body. It helps regulate the immune system.

The idea is to use the genetically engineered tumor cells to stimulate the body into recognizing the malignancies as "foreign" invaders and to spur the immune system into attacking and destroying tumors throughout the body.

In announcing the experiment, NIH Director Bernadine Healy predicted that the study "will pioneer a new approach to gene therapy in cancer."

The human body is capable of provoking an immune response against cancer on its own, but typically it is weak. By genetically priming tumor cells to pump out large quantities of tumor necrosis factor, Rosenberg and his NCI team hope to hasten destruction of the malignant cells.

"What we're trying to do now is immunize the whole body against cancer," Rosenberg said in an interview. "When we reinject the cells, we hope this will marshal the immune reaction around that cancer so that the body becomes 'immunized' against it, and the immunization spreads throughout the body."

The ultimate application could be to use such therapy early after cancer detection. For example, it could be employed "to treat somebody after surgery and use this to prevent the cancer from coming back," Rosenberg said. "But that's in the future."

Rosenberg emphasized that the work "is still highly experimental" and not available or ready for general use. "It's just a start," he said, adding that it probably will be one or two years "before we know if the approach is valuable."

The injection of a substance associated with a disease--in this case, cancer--to enhance the body's own immune responses to that disease is common to all immunization theories.

Studies of mice treated with genetically altered tumor cells have shown that their cancers grow for a short time and then spontaneously shrink and disappear--leaving the mice immune to the tumor, NIH said.

NCI researchers hope to achieve a similar result in humans, NIH said.

Rosenberg noted that calling the substance a "vaccine" is a misnomer, since "to a lot of people, vaccine means preventing a disease--which is not what we're doing." Nevertheless, the term has popularly been used to describe the approach.

Rosenberg and other experts said that human studies using other so-called "cancer vaccines" that have not used similar immune system stimulants have shown mixed or disappointing results.

Rosenberg and his team also plan to conduct the same experiment using the gene for the production of interleukin-2, another immune system substance that stimulates the body's tumor-fighting lymphocytes, or cells.

Three weeks after the "immunization," the patient's lymph nodes will be removed near the immunization site in the thigh to harvest additional immune system cells there, and to remove any tumors that might have formed. Rosenberg said that he believes that cells in this region may be "the most potent anti-tumor fighters the body has to offer."

These will be cultivated to produce greater numbers of cells which will then be re-infused back into the patient "as an added punch which takes advantage of the immunization," Rosenberg said.

The latest study is a logical continuation of Rosenberg's ongoing research, which has involved genetically manipulated attempts to beef up the body's existing immune defenses against cancer.

Last January, in a different experiment, he and his team took special cancer-killing cells naturally produced by the immune system--known as tumor infiltrating lymphocytes--that also had been genetically altered with tumor necrosis factor. These were transfused back into the patient. The idea was to use these doctored cells as a kind of "drug" therapy to destroy tumors. This work is continuing but it is considered too early to evaluate the results.

Unlike standard cancer treatments, such as radiation and chemotherapy, which can wipe out healthy as well as diseased cells, the new approach is designed to zero in only on malignant growths.

"I think that human gene therapy is opening up a new era of medical research that will have payoffs in cancer and many other diseases in the years to come," said Dr. John Laszlo, senior vice president for research of the American Cancer Society. "We're just at the foothills of what might be the Himalayas with our knowledge--but you have to start there."

The experiment began less than 24 hours after Rosenberg received a go-ahead from the Recombinant DNA Advisory Committee, a key NIH advisory committee whose members must approve such research before it can proceed. Healy gave her approval Monday evening.

Rosenberg said that he plans to treat a second patient Friday, a young woman also suffering from melanoma.

Rosenberg has received permission to treat 30 patients and intends also to use the therapy in patients with advanced colorectal and kidney cancers.

Advertisement
Los Angeles Times Articles
|
|
|