Study finds potential way to improve cancer immunotherapy

Drugs that contain antibodies are a standard part of therapy for many cancers, but these antibodies do not always work. A finding by researchers with the Holden Comprehensive Cancer Center at the University of Iowa may help make the antibodies more effective by boosting the power of white blood cells, which play a role in fighting cancer.

One way that antibodies ideally function is to stick to cancer cells and signal various types of white blood cells to kill the cancer cells. The UI Holden Center team and colleagues used mouse cell lines that mimic human conditions to learn how different types of white blood cells work with antibodies and contribute to killing cancer cells. The team used different classes of an immune stimulant known as CpG ODN (CpG oligodeoxynucleotide) to encourage different types of white blood cells, either separately or together, to work with antibodies to kill cancer.

The new information could help doctors make antibodies more effective by providing a way to gear up specific types of white blood cells — natural killer cells and granulocytes — at the same time that patients receive a dose of anti-cancer antibodies, said George Weiner, M.D., UI professor of internal medicine, director of the Holden Comprehensive Cancer Center and principal investigator for the study. The findings appear in the Sept. 1 issue of the journal Cancer Research.

“Previous research suggested that different white blood cells can kill cancer cells,” Weiner said. “We found that by selecting other agents as stimulants, we can specially direct one type or another of white blood cells to do the killing. It’s an extra measure of control for the white blood cells that you specifically want to activate to destroy the cancer cells.”

Weiner said the finding potentially could lead to improved therapies for patients. The UI currently is evaluating this approach in clinical trials.

Monoclonal antibodies currently used in cancer therapies include rituximab (Rituxan) for certain types of non-Hodgkin’s lymphoma and trastuzumab (Herceptin) for breast cancer.

People do not normally have these antibodies in their system. The cancer-fighting versions are based on natural antibodies and designed to react with cancer cells, Weiner said. With cancers, the immune system fails to recognize tumors as invaders — that is where drugs can step in and make a difference.

“Using antibodies is a way of taking the immune system and redirecting it toward killing the cancer,” Weiner said.

Non-Hodgkin’s lymphoma is cancer of the lymphatic system, which normally fights infection. The lymphatic system includes lymph nodes and parts of the body that include lymphatic tissues: the spleen, thymus gland, bone marrow, adenoids and tonsils.

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Contributors to the study included investigators at the University Medical Center Utrecht in the Netherlands.

Funding for the study included a Specialized Programs of Research Excellence (SPORE) grant from the National Cancer Institute (NCI). For information on that grant, visit http://www.uiowa.edu/~ournews/2002/september/0918SPORE.html. The study also included support from Coley Pharmaceutical Group. Weiner serves as a consultant for Coley.

The Holden Comprehensive Cancer Center is Iowa’s only National Cancer Institute (NCI)-designated comprehensive cancer center. NCI-designated comprehensive cancer centers are recognized as the leaders in developing new approaches to cancer prevention and cancer care, conducting leading edge research and educating the public about cancer.

University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at www.uihealthcare.com.