Vaccine Study for Brain Tumours Targets Multiple Antigens

A new vaccine approach being studied at the University of Pittsburgh Cancer Institute (UPCI) is using multiple antigens to bring about an immune response to brain tumors, or gliomas – highly lethal, primary tumors that are difficult to treat successfully since they aggressively invade the folds and creases of the brain. In the study, four different antigens, proteins found on the surface of tumor cells, are modified to look more dangerous, potentially soliciting a strong response by the immune system’s dendritic cells. These cells act as the quarterbacks of the immune system and coordinate the system’s attack against foreign invaders.

The project, headed by researcher Hideho Okada, M.D., Ph.D., assistant professor of neurosurgery and surgery at the University of Pittsburgh School of Medicine, is based on an “off the shelf” vaccine approach in which antigen peptides are synthesized and ready to use when needed. Once the peptides have been synthesized, the vaccine is introduced to glioma cells in the body.”We developed our vaccine based on four different tumor antigens that are commonly found in glioma tumors,” explains Dr. Okada. “This is a much more practical approach than creating vaccines from a patient’s own tumor cells because of the limited life expectancy of patients with brain tumors. By the time you have cultured a patient’s own vaccine cells, a process that can take up to six weeks, the patient’s cancer has already progressed to the point where there is nothing more we can do clinically. We see our approach as a more practical and potentially life-saving one.”To synthesize the antigen peptides, Dr. Okada and his team create modified peptides that are capable of activating an immune response by combining them with a class of helper peptides and dendritic cells. The dendritic cells are loaded with information about the tumors cells so that they will communicate to the T-cells to attack once the vaccine has been introduced to the body. The goal is that the modified antigen peptides will be recognized by the immune cells and elicit a strong immune response.Given that all brain tumors are different, as are their immune responses, Dr. Okada believes a multi-antigen approach has the best potential for success. “One of the benefits to testing multiple antigens is that you will be less likely to miss your target and more likely to get a response,” he said.Dr. Okada adds that given the lack of effective treatments for brain tumor patients, immunotherapeutic approaches have a real potential for success because of the ability for immune cells to migrate into the central nervous system and selectively destroy malignant cells that have infiltrated tissue there.Malignant gliomas make up the majority of primary brain tumors and cause the deaths of more than 12,000 brain cancer patients each year. One of the most common gliomas, glioblastoma multiforme, has an average survival of only 12 months. Standard treatments, such as chemotherapy and radiation, are difficult to use successfully without damaging the surrounding healthy brain tissue.(Source: University of Pittsburgh: February 2006.)