New weapon in cancer war
3/4/2001When you want something done, you might as well do it yourself.
That seems to be at the heart of cancer therapy trials going on at the Medical College of Ohio.
The new treatment under evaluation has at its base an emerging technology that uses what the body has been trying to do for itself all along. The researchers hope that by boosting nature's own cancer warriors, there may be a victory somewhere in the future.
Scientists are testing a vaccine against recurring and often fatal ovarian cancer.
Ovarian cancer has proven difficult to conquer because it's rarely caught early.
“Most women in America present with advanced-stage disease of ovarian cancer,'' said Dr. Stephen Andrews, a gynecologist-oncologist and principal investigator for the MCO vaccine trial.
“There is no screening test, and there are no early signs or symptoms for ovarian cancer, so probably about 75 percent of women in the U.S. are in advanced stage at diagnosis,'' he said.
“In many women, their actual first symptom is, suddenly, their belly will puff way out. Your pants don't buckle. The reason is the abdomen is filled with fluid,'' he said.
Generally, women are treated through surgery and chemotherapy. While that works for 60 to 70 percent of ovarian cancer patients, “Most of these women will relapse within three years. There obviously must already be some resistance to the first line [chemotherapy] drugs,'' Dr. Andrews said.
Ovarian cancer is the fifth most common cancer diagnosis among women, and the No. 5 cause of cancer deaths. More than 25,000 new cases were diagnosed in 1999, and nearly 15,000 American women died that year from ovarian cancer, according to the National Cancer Institute.
While the term “vaccine” summons up the idea of shots for polio or chicken pox, cancer vaccines are not yet preventive medicine in the same sense. While the goal is eventual development of a vaccine to prevent cancer, thus far they're only used after someone develops the disease. A patient's own tumor cells are fashioned into a personal messenger to wake up a lagging immune system.
Dr. David Berd of the Thomas Jefferson Medical College in Philadelphia developed this cancer vaccine and used it successfully against melanoma. In clinical trials, survival rates among 37 patients whose melanoma had spread to various internal organs nearly doubled. Sixty percent of the patients with this very advanced cancer survived an average of 27 months, compared to the historical survival rate of 15 months without the vaccine.
The melanoma vaccine is completing large-scale trials. If it continues to perform well, and meets U.S. Food & Drug Administration standards, it could hit the U.S. market in two years. The drug is already on sale in Australia, where drug regulations differ, and will be introduced in Europe later this year.
Kansas City-based Avax Technologies, Inc., licensed the vaccine from the Philadelphia medical college in 1995. Dr. Berd has an equity stake in the company and serves as chairman of its scientific advisory board.
In the ovarian cancer trial that began last month at MCO and several other centers, doctors will take a tumor cell sample from every newly diagnosed ovarian cancer patient who agrees to participate in the trial.
The tumor cells are sent to a laboratory in Philadelphia. There the cells are separated from one another and “mixed with an immune system booster to really rev up the immune system,'' said Dr. Donald Braun, administrative director of the MCO Cancer Institute and a professor of surgery.
The booster is called DNP, dinitrophenyl, a chemical that sticks to the tumor cells and incites the immune system to attack.
“It's a principle that's been known for maybe 50 years, a trick to get animals to make an immune response,'' said Dr. Berd. But it wasn't until he devised this recipe for cancer that DNP was included in a vaccine.
If a cancer patient's tumor recurs within the 12-month research period, her frozen cells will be returned to MCO to be defrosted and killed with radiation. Once killed, the cells are no longer a danger to the patient, but remain recognizable to the immune system.
Finally, the cells are mixed with a second immune stimulant, a killed bacteria known as BCG - bacillus Calmette-Gu rin - and injected into the patient every week for six weeks. At six months, the patient receives a booster shot.
The tumor vaccine is not unlike a vaccine against polio or measles. The cancer-comprised immune system was no longer efficiently fighting tumor cells. But once it sees the souped-up vaccine cells, it learns to recognize both vaccine cancer cells and the patient's cancer cells as enemies.
But there's a hitch. The immune system's animosity toward the native cancer cells is never as aggressive as its attack on vaccine cells.
In melanoma vaccine trials, it was evident that patients who faired best with vaccine therapy were those who still had some natural immune response to their own cancers. In early trials of the ovarian cancer vaccine, about half the patients still exhibited some natural immune response, Dr. Berd said.
Research on cancer vaccines got their big push in the 1950s, and by the 1970s “people thought it would be a piece of cake,'' Dr. Berd said. But successful vaccines in mice never translated into successful vaccines for humans, and researchers abandoned the quest in droves. Dr. Berd, who entered the field in the 1970s, is one of the few who stuck with it during the long, dry season.
Today, at least 50 institutions have ongoing cancer vaccine research, as the field is hot again due to advances in biotechnology. Research is under way for vaccines against a variety of cancers including prostate, kidney, breast, lung, and colorectal.
In early trials of the ovarian cancer vaccine, “we've had a couple of patients benefit,'' said Dr. Berd. One of the 25 patients' tumors shrunk during the trial, and several others saw a drop in the amount of something called CA-125 in their blood. CA-125 is a marker for ovarian cancer. About 80 percent of women with the disease have elevated levels of this antigen.
The cancer vaccine trial will eventually involve 15 to 20 women at MCO for a total of 400 nationwide. While this first vaccine trial is limited to women newly diagnosed with ovarian cancer, other trials in the pipeline will include women with recurring disease whose initial diagnosis did not take place at MCO. Other tests will pit the vaccine against the chemotoxic agents normally used against recurring ovarian cancer.
The success rate for those chemotherapy drugs is between 15 and 30 percent, Dr. Andrews said.