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, MD, 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, MD, PhD, 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.MORE