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William Chambers, Ph.D.

William Chambers, Ph.D.

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McDonnell Foundation Awards University Of Pittsburgh Professor For Innovative Project On Immunotherapy Of Brain Cancer

PITTSBURGH, December 4, 2001 — William Chambers, Ph.D., associate professor of pathology at the University of Pittsburgh School of Medicine, has received a $450,000 award from the James S. McDonnell Foundation through its 21st Century Science Initiative. The award program annually funds researchers pursuing challenging and important projects that will likely advance the current state of scientific knowledge in treating brain cancer.

Dr. Chambers, a member of the University of Pittsburgh Cancer Institute(UPCI)’s Immunology Program and Brain Tumor Center, was one of three researchers nationally who received the award this year.

The focus of Dr. Chambers’ research is on the treatment of gliomas, which are highly lethal, primary brain tumors. At present, these tumors are very difficult to treat successfully. Malignant gliomas make up the majority of primary brain tumors and will cause the deaths of approximately 13,000 brain cancer patients this year alone.

“A brain tumor diagnosis can be devastating for a patient,” said Dr. Chambers. “I am hopeful that pursuing promising, new approaches to treating gliomas can translate into vast improvements in treatment, and possibly even cures.”

Gliomas tend to aggressively invade the folds and creases of the brain around the tumor, making them difficult or impossible to completely remove surgically. Similarly, with standard treatment such as chemotherapy and radiation, it is difficult to treat the tumor successfully without damaging the surrounding healthy tissues. Because of the limitations of standard therapies, Dr. Chambers is exploring gene therapy-based, immunological approaches that activate and maintain the function of the anti-tumor immune response.

“While there is evidence that immune cells, such as lymphocytes, infiltrate gliomas, they are generally ineffective in fighting the tumor’s growth and development,” said Dr. Chambers. “Many analyses have indicated that the function of lymphocytes is suppressed in gliomas, as is the function of the immune system throughout the body in patients with gliomas. Our hope is that we can correct and improve the function of the immune response to these tumors and use this to target the infiltrative areas of gliomas that are difficult to eliminate using standard therapies.”

Dr. Chambers will be combining two therapeutic approaches that individually have produced promising, but limited, results. He proposes that coupling the therapies will create an advantage to either approach as a single therapy. The combined approach, called RICS therapy, or the reversal of immunosuppression coupled with cytotoxic cell stimulation, attempts to induce an effective immune response by blocking the function of tumor-derived transforming growth factor-b (TGFb). TGFb is a protein produced by gliomas that is responsible for much of the immune suppression associated with these tumors. The approach also seeks to stimulate cytotoxic lymphocytes, which include natural killer (NK) cells and T cells, to destroy the gliomas. Dr. Chambers will be working with hormones produced by the immune system called cytokines to stimulate these cells. One in particular, interleukin-12 (IL12), activates the anti-tumor effects of both NK cells and T cells and has been shown to promote anti-glioma immunity.

“Because there have been some successes with both of these approaches, combining them holds promise for an improved response,” said Dr. Chambers. “It is my belief that there is great potential for combined approaches, which will almost surely provide far more effective treatment than any single therapy. Our goal is to start with a preclinical model and if successful, translate the approach into clinical practice as soon as possible.”

Founded in 1950 by aerospace pioneer James S. McDonnell, the McDonnell Foundation was established to “improve the quality of life,” and does so by contributing to the generation of new knowledge by supporting research and scholarship. Since its inception, the McDonnell Foundation has awarded more than $218 million in grants.

As the only National Cancer Institute-designated comprehensive cancer center in western Pennsylvania, UPCI is a recognized leader in providing state-of-the-art cancer prevention, detection, diagnosis and treatment services; bio-medical research; patient care and support; and community outreach services. UPCI investigators are world-renowned for their work in clinical and basic cancer research.

For more information on brain cancer, contact UPCI’s Cancer Information and Referral Service at 1-800-237-4PCI (1-800-237-4724), or visit UPCI’s website at www.upmccancercenters.com.

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