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Dangerous Side Effect Found in Cancer Immunotherapy Research
Date:6/3/2008

Lab experiment resulted in T-cells spreading beyond treatment area

TUESDAY, June 3 (HealthDay News) -- When scientists first began looking into using the body's own immune system to target malignancies, it was hoped that the therapy would be able to zero in on a specific cancer without affecting healthy tissue.

While the original theory is still worth pursuing, researchers have found some potentially harmful side effects.

The findings, published in the June 10 issue of the Proceedings of the National Academy of Sciences, concluded that a skin cancer immunization therapy created a dangerous consequence.

"The ultimate lesson to be learned from this report is that all treatments have potential side effects, and we have to be very thoughtful about potential side effects," said Dr. Louis M. Weiner, director of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, D.C. "We have to be very thoughtful about how we apply those treatments, who we apply those treatments for, and how we follow the patients we treat to assure appropriate safety."

Cancer vaccines are developed to stimulate the body's own immune system to fight off deadly cancers. Ideally, the target of the vaccine will be very specific to the tumor, but this is not always the case: Antigens, or molecules that provoke antibody production, that are found only on the tumor are usually found also only in individual patients. Other antigens are shared between patients but are also found in normal cells, leading to the possibility that the vaccine will kill healthy cells along with malignant ones.

The investigators on this study, from the National Cancer Institute, plucked T-cells from the bloodstream of mice, cultured the cells in the lab to mount a response against a melanoma-related target, GP10, then re-injected the T-cells into the mice to fight the cancer. Melanoma is a particularly lethal form of cancer that starts on the skin.

Such a therapy can cause depigmentation of the skin and, sometimes, attacks on the thyroid.

"Those problems tend to be irritating but not life-threatening, and if they are the price that one has to pay for a cure or highly effective treatment for a highly deadly disease, most patients are willing to pay the price," Weiner said.

But in this particular investigation, the eye also became a target. "That carries with it more profound consequences, although they could inject steroids into the eye that would kill the T-cells in the eye," Weiner said. (This would produce a local effect only and would not affect the melanoma treatment itself.)

"As we develop increasingly more effective immune therapy strategies that are capable of attacking self, be it a self-tumor or self-normal organ, there may well be potentially surprising prices to pay in terms of toxicities," Weiner said. "The authors suggest that understanding the consequences of new immunotherapies for cancer should help researchers guide future treatments and anticipate and treat side effects, thus preventing healthy cells from getting caught in the crossfire."

More information

Learn more about cancer vaccines at the National Cancer Institute.



SOURCES: Louis M. Weiner, M.D., director, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C.; June 10, 2008, Proceedings of the National Academy of Sciences


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