Giving the Immune System a Second Chance to Kill Cancers

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April 30, 2001 (Dana Point, Calif.) -- A bold new treatment for an incurable cancer will give the immune system a second chance to fight the disease.

The immune system is supposed to get rid of cancer cells before they grow into large tumors. But by the time a tumor develops, the immune system usually has given up the fight. A major goal of modern cancer research is to put new life into the body's natural antitumor defenses.

"We think we need the proper type of fertilizer," says Ivan Borrello, MD, assistant professor of oncology at Johns Hopkins University. "The problem is that these tumor cells are growing in the context of our own immune system, and the immune system is no longer effective in fighting it. What happens is we get tolerance. The [antitumor] arm of the immune system just ignores the tumor and lets it go. Our challenge is to overcome this."

Borrello's team is working with patients who have multiple myeloma -- a disease in which certain blood cells -- the plasma cells -- become malignant. It's a relatively common disease, accounting for one out of every 100 cancers in the U.S. There is no cure. Most patients get lots of chemotherapy, which helps, but most people survive only three years.

Traditionally, doctors give the immune system a second chance to fight multiple myeloma by wiping out the immune system with intense chemotherapy, and then replacing it using a bone marrow transplant. The transplant itself goes well if it uses a person's own bone marrow, harvested just before the chemotherapy. The technique -- called autologous bone marrow transplantation -- can extend survival by 14 months or more, but soon the same thing happens: the new immune cells stop fighting the cancer and it returns.

If a relative's bone marrow is used instead of the patient's own bone marrow, the immune responses that come back are more aggressive. A few patients have been cured in this way. But this chance to beat the cancer comes at a frightening cost -- up to 40% of patients don't survive the operation because the other person's immune cells attack their new host.


Borrello thinks he has a better idea. He plans to take a patient's own tumor cells, irradiate them until they are dead, and -- very soon after autologous bone marrow transplant -- use them to vaccinate the person against the tumor.

The new treatment seems crazy -- it's supposed to prime the immune system to fight cancer by giving a person a vaccine just after his or her immune system has been wiped out by potent chemotherapy. But it works in mice, and Borrello thinks it will work in people, too.

For one thing, the killed tumor cells have a large number of immunity-inducing antigens clinging to their surface. Antigens are the substances in the body that trigger the immune system to fight disease and infection. Most researchers believe that effective cancer vaccines should include this kind of wide-ranging assortment of ingredients.

"A single tumor cell may express many different tumor antigens," says cancer vaccine expert Walter Storkus, PhD, of the University of Pittsburgh. "The most effective tumor vaccines should promote diverse immune responses."

And for another thing, giving the vaccine to people just as their immune systems are beginning to come back could tell the newborn immune cells that the tumor is an enemy and not something they should ignore.

In a clinical trial scheduled to begin this week, 15 patients will have both multiple myeloma tumor cells and healthy bone marrow removed from their bodies and stored until later. They then will have their immune systems destroyed by chemotherapy and restored by retransplant of the bone marrow. Then they will get multiple injections of the tumor cells mixed with a natural immunity-enhancing substance. They will get as many as 25 under-the-skin injections (depending on how many tumor cells the researchers could harvest) every month for a year, and then every two months for four more years.

"We're going to try to enhance the cure rate in multiple myeloma," Borrello says. "The critical aspect is figuring out how to turn the immune system on. ... Clearly what is needed in this disease is to get out of the box of giving more and more chemotherapy."


This vaccine approach has been patented by the company CellGeneSys, which is sponsoring the clinical trial.

WebMD Health News Reviewed by Gary D. Vogin, MD
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