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Winter 2010

Promising Vaccine Being Tested to Fight Brain Cancer

12/21/2009

VS Winter 2010-Promising VaccineThe death of U.S. Sen. Edward Kennedy brought to the public’s attention the severity and tragedy of brain tumors. Sen. Kennedy had what is known as a glioblastoma, the most common and deadly form of glioma — the average survival rate of people diagnosed with a glioblastoma is between 12 and 18 months. Glioblastoma also is the form of cancer that UCLA neurosurgeon Linda Liau, M.D., Ph.D., is tackling in her research. Dr. Liau, director of the UCLA Brain Tumor Program, and her colleagues have developed a promising vaccine against brain cancer that is currently in Phase II clinical trials.

Why are brain tumors so difficult to defeat?
Dr. Liau: Glioblastomas, the most common type of malignant brain tumor, grow very fast and can quickly spread to other areas of the brain. So even with surgery, radiation and chemotherapy, most malignant brain tumors will return because it is impossible to remove every cancerous cell.

You are the principal investigator of a clinical trial to test a brain cancer vaccine you and your colleagues have developed. How does the vaccine work?
Dr. Liau: In the lab we manufacture the personalized brain cancer vaccine from two components. First, we take proteins (antigens) from the actual tumor of the patient. Next, we take some of the patient’s white blood cells, called dendritic cells, which are antigen-presenting cells that circulate in the blood. Dendritic cells are essential for the start of any immune response, be it against a bacterial infection, a viral infection or tumor cells. Moreover, these dendritic cells are also responsible for telling the body what type of immune response to initiate, so that the invader can be attacked with the most effective tools.

VS Winter 2010 - Dr. LiauOur brain cancer vaccine harnesses the power of these immune cells by preparing them outside the body and putting them in direct contact with brain-tumor proteins. Once we have separated the dendritic cells, we load them with the extracts of the tumor cells. The loaded dendritic cells are then injected back into the patient, where they behave like they just encountered an infection; they travel to the lymph nodes to tell the immune system about the tumor cells. The ensuing activation of the immune system results in the generation of killer T cells that travel through the body. If these cells encounter a tumor cell, they will recognize and kill it. Hopefully, in this way, immunization with the brain cancer vaccine helps control the outgrowth/ recurrence of the tumor.

Several different vaccines are being tested for various cancers. Is there anything that makes your vaccine unique?
Dr. Liau: Because of the blood-brain barrier, brain cancer vaccines face unique challenges. Several aspects make our vaccine unique among the cancer vaccines that are now in late-stage clinical trials. Our vaccine, for example, uses live cells, actual dendritic cells, rather than some other cell types, such as modified tumor cells, that are being used in other vaccines. The concentration and purity of our dendritic cells is very high. Because of the blood-brain barrier, dendritic cells usually do not encounter tumors in the brain;
therefore, we use the actual tumor-cell extract from the patient to make sure that the immune system is properly directed.

Is the vaccine individual to each patient? Does that make the vaccine relatively expensive?
Dr. Liau: Yes, the vaccine is customized for each of our patients. We are able to keep the cost down by manufacturing a full course of treatment for a patient in a single manufacturing run. Such a full course of treatment typically is sufficient to treat a patient for over a year.

Is there enough data collected yet on your brain vaccine to get patients or researchers excited about the vaccine?
Dr. Liau: There is some excitement about it from both groups. The data that we have collected to date in our Phase I clinical trials looks very promising in terms of prevention or delay of tumor recurrence, as well as extension of survival. A high percentage of people who have been treated with the vaccine in the Phase I trial have so far shown no evidence of tumor regrowth, even years after their original surgery. This is quite unusual for patients with this aggressive brain disease (glioblastoma). However, further Phase II multi-center randomized trials (which are currently underway) will be needed to prove true efficacy.

What, if any, challenges exist for the vaccine in the future?
Dr. Liau: Clinical development and testing of a new product is a challenging, long-term and expensive endeavor. We will need to continue our clinical testing, and for that we will have to continue to educate people, including government regulators and those in the financial markets, about this new and promising approach to the treatment of cancer. Other than that, it just comes down to a lot of hard work and waiting for the results of our ongoing Phase II/III randomized clinical trials.

To read more about Dr. Liau and her work, go to:
www.uclahealth.org/thesurgeonscientist





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