Brain Tumor Vaccines

Published in the National National Brain Tumor Society's quarterly newsletter Search

Linda Liau, MD, PhD is a neurosurgeon and Professor of Neurosurgery at the UCLA School of Medicine. She is also the Director of the Comprehensive Brain Tumor Program and Director of Neurosurgical Oncology at the UCLA Medical Center in Los Angeles. An expert in the field of immunotherapy and lead investigator in a multi-center vaccine trial for newly diagnosed brain tumors, Dr. Liau spent some time with us recently answering our questions about brain tumor vaccines.

How do brain tumor vaccines work?
Brain tumor vaccines are still in the experimental phase of clinical application. The idea is that they will work by enhancing the body’s own immune response against the tumor, so that a person’s own immune cells (T cells) will circulate and prevent a tumor from recurring. A brain tumor vaccine should work similar to vaccines against illnesses like measles and chickenpox. However, instead of giving patients a weakened version of a virus, we would give them a low dose of a tumor antigen. Antigens are proteins from the surface of tumor cells that stimulate an immune response. We would be teaching the body to recognize the tumor as foreign so if it recurs, the body can fight it.

What are the latest developments in brain tumor vaccines?
There are hundreds of pre-clinical trials underway right now, and most exciting, there are several clinical trials ongoing. Two of these are multi-center Phase 2 and 3 trials, which means they have passed the “proof of principle” exploratory phase and are being tested for efficacy in randomized controlled trials. One of these is a trial of a vaccine for glioblastoma, which we developed here at UCLA, in which we take antigens from the patient’s own tumor and combine them with their own antigen-presenting immune cells (also called dendritic cells) to create a vaccine to induce an immune response. The other major ongoing multi-center trial is taking a particular antigen called EGFRvIII that we often see in glioblastomas and treating patients with tumors that have that same antigen.

Has the idea of a brain tumor vaccine been explored in the past?
Some clinical trials were done in the 1980s with people who had very advanced-stage brain tumors, and that research did not get very far beyond exploratory pilot trials. Although there still is a lot to learn, we have a much better understanding of the immune system now. We’ve identified a lot of target molecules that we didn’t know about then, and we have better genetic and molecular characterizations of them. We also know that there are different types of T cells, some of which are good and some are bad. A lot has happened in the field of immunology and that has changed many people’s perspectives on the idea of cancer vaccines. And of course, there is now an FDA-approved vaccine for cervical cancer, so we know that cancer vaccines can work.

How do you think brain tumor vaccines will be used?
I believe that vaccines will work best when used to prevent brain tumor recurrence, not necessarily to rid the body of a large, bulky, actively growing tumor. That means we would want to use a vaccine once a brain tumor has been surgically removed and we have followed up with radiation and chemotherapy. The goal of the vaccine would be to prevent recurrence, which is really the biggest problem with brain cancer. I think vaccines will be used in conjunction with other therapies, the way that chemotherapy is used in conjunction with surgery and radiation today.

What is the most exciting area of vaccine research?
I think individualized patient vaccines and treatments are a very exciting prospect. As we learn more about the genetic makeup of brain cancers, it seems that all patients and all tumors are not the same. We are not going to have one treatment for everybody; I think we will see more personalized, individualized medicine in terms of both targeted drug therapies and personalized vaccines—and probably a combination of all of the treatments we’ll have available.

How might vaccines interact with other therapies?
In our lab, we are investigating how chemotherapy drugs interact with immune responses. We used to ask patients not to undergo chemotherapy before receiving a vaccine because we thought the chemotherapy would be immunosuppressive. But now we’re seeing that there are good and bad T cells, and it might not be a bad idea to knock down the bad T cells with targeted drug therapies. Also, there are some drugs now that can enhance the antigen expression on tumors, making them easier for a body’s immune system to recognize them.

What impact do you hope your research will have?
As a physician as well as a researcher, I’m hoping that my patients will live longer and have good quality of life—that’s one appeal of vaccine therapy, that the side effects are relatively minor.