UPCI Physicians Begin Study Of IL-4 Producing Cellular Vaccine For Brain Tumors

PITTSBURGH, February 24, 2000 — Researchers at the University of Pittsburgh Cancer Institute (UPCI) have begun a phase-I clinical study using a genetically engineered anti-tumor vaccine to treat brain tumors, which strike more than 17,000 people a year in the United States.

"Malignant gliomas, the most common type of primary brain tumors, are highly lethal," said Ian Pollack, M.D., principal investigator of the study, professor in the department of neurological surgery, and co-director of UPCI’s Brain Tumor Center. "This study is a very important one because it addresses a possible method of treating these cancers, which often return quickly after standard therapies, such as surgery. Immunotherapy is a promising, yet unproven, treatment for this class of cancers."

"The research involves a transfer of a gene for Interleukin-4 (IL-4), which increases the immune response against malignant gliomas, as well as a herpes simplex virus-thymidine kinase (HSV-TK) gene, a suicide gene," said Hideho Okada, M.D., Ph.D., study co-investigator, assistant professor of neurosurgery and co-director of the Vector Core Laboratory at the University of Pittsburgh Center for Biotechnology and Bioengineering. The procedure begins by removing brain cells from a patient undergoing brain tumor "debulking," whereby a surgeon removes as much tumor as possible. These cells are then exposed to a retrovirus carrying genes for IL-4, HSV-TK and a special marker gene. The cells are cultured, and the researchers use the special marker gene to select those cells that have picked up the viral vector/gene package. These cells are then purified and injected underneath the skin in the leg of a patient. It is thought that the introduced IL-4 gene causes the tumor cell "vaccine" to produce IL-4, which attracts specialized immune cells to process the tumor cells and, in turn, stimulate other immune cells to recognize and attack tumor cells within the vaccine site and also within the brain. The genetically modified cells also will produce HSV-TK, an enzyme that is not normally produced by the body. Cells that make HSV-TK can be killed with a drug called gancyclovir, which will be administered to patients about eight days following this experimental treatment. In this way, doctors allow the body’s immune system time to recognize the tumor cell to boost the body’s anti-immune response, yet they provide a mechanism whereby the reintroduced tumor cells carrying the IL-4 and HSV-TK genes are destroyed.

Current treatments for patients with the most common primary brain tumors are unsatisfactory, with most patients suffering recurrence of the tumor, according to study co-investigators David Schiff, M.D., assistant professor of neurological surgery, neurology and medicine, and Frank Lieberman, M.D., associate professor of neurology and medical oncology. Thus, this experimental therapy may prove more effective in that respect as well.

"This study is very exciting because IL-4 gene therapy has important biological properties in cancer immunology," said Michael Lotze, M.D., professor of surgery, molecular genetics and biochemistry.

"It’s not easy to cure brain tumors even in animal models, but this experimental therapy has proven to be very effective in animals," Dr. Okada said.

Eligible patients for this study must have operable brain tumors and be weaned from treatment with steroids, which can suppress immunity that IL-4 is supposed to stimulate.

For more information about this study, please call Mary McLaughlin, R.N., at UPCI’s Brain Tumor Center at 412-647-5369. Patients participating in the study will be evaluated and experimentally treated in UPCI’s Brain Tumor Center under the care of Drs. Lieberman and Schiff.

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

For additional information on UPCI, please access http://www.upmccancercenters.com.