Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: WEDNESDAY, May 23, 1990 TAG: 9005230472
SECTION: NATIONAL/INTERNATIONAL PAGE: A9 EDITION: METRO
SOURCE: Associated Press
DATELINE: WASHINGTON LENGTH: Medium
The preliminary study, conducted on seven patients, is the first approved attempt at human gene therapy - inserting potentially helpful genes inside the body in places where nature failed to put them.
The experiment was intended to show that the approach was possible. Physicians introduced a bacterial gene that had no effect on the patients' cancer.
Soon, however, they plan to equip patients' blood cells with a gene that delivers a powerful natural cancer-killing substance known as tumor necrosis factor. The researchers hope that will cure the disease by blitzing the tumor with extremely high levels of toxic proteins.
"This is the first study in which foreign genes have been introduced into humans with survival of those cells," said Dr. Steven A. Rosenberg. "This is meant to pave the way to introducing genes that can improve the survival of cancer patients."
His pilot study showed that not only did the cells survive, they homed in on tumors and produced a foreign protein there.
Rosenberg outlined his results at the annual meeting of the American Society of Clinical Oncology. A more detailed report is scheduled to be published in the New England Journal of Medicine.
Dr. Robert Young of Philadelphia's Fox Chase Cancer Center noted that while biologists have isolated genes that make potentially useful substances, transferring that knowledge from the petri dish to cancer patients has been difficult.
Rosenberg, a National Cancer Institute researcher, developed a cancer treatment known as adoptive immunotherapy intended to harness the body's own cancer-fighting chemicals to control the disease.
His first results, using the protein interleukin-2, attracted wide attention when they were announced five years ago. Follow-up research showed only a small minority of patients, perhaps 5 percent to 10 percent, respond with complete reversal of the disease.
The latest work is an attempt to boost the power of those natural chemicals by delivering them directly to the tumor. At Tuesday's meeting, Rosenberg described the results of experiments over the past year on his first five patients.
First, doctors removed so-called tumor-infiltrating lymphocytes from each patient. Those are cancer-hunting white blood cells that had invaded the tumors of patients dying of melanoma, a form of skin cancer.
Then, doctors isolated a gene that gives bacteria the ability to resist the antibiotic neomycin. They put that gene into a crippled virus, which in turn carried it into the patients' white blood cells.
Finally, they multiplied the blood cells in test tubes with interleukin-2, a growth hormone, injecting 200 billion of those cells into each patient.
Because the cells carried a bacterial gene, doctors could track them through the patients' bodies. They found that the manipulated cells persisted in the blood for up to 189 days.
They performed biopsies on two patients and found the cells in the tumors, making the bacterial protein, 64 days after the injections.
All of the patients treated were expected to die within three months. Two of them responded well to the boosted levels of tumor-infiltrating cells, and the melanoma has disappeared in one completely for 10 months.
Rosenberg said the experiment worked just as his team had hoped.
"There were no surprises in this," he said. "I am looking forward to trials that hopefully will help cancer patients."
He said he and colleagues had already succeeded in inserting the gene that makes tumor necrosis factor into human blood cells. Those cells make 100 times higher levels of the protein than are ordinarily present.
Rosenberg said he hoped to win approval within a few months from several regulating committees so he can try the next step on melanoma patients.
by CNB