Featuring: Catalina Lee Chang, PhD and Maciej Lesniak, MD
Northwestern investigators have developed a novel vaccine that utilizes a specialized group of B-cells to promote anti-tumor immunity against glioblastoma, according to findings published in the Journal of Experimental Medicine.
The vaccine, which is still in pre-clinical stages, is the first of its kind and may be an alternative to currently available immunotherapeutic approaches to treat the fatal brain cancer, according to Catalina Lee Chang, PhD, research assistant professor of Neurological Surgery and first author of the study.
Glioblastoma, the most aggressive type of brain cancer, can occur at any age but most commonly develops in adults. The cancer has no cure and life expectancy after diagnosis can range anywhere between 12 to 24 months, depending on the timing and frequency of treatment.
Over the last 30 years, immunotherapy has become an effective option in helping the immune system fight various types of cancer. Unfortunately, however, most patients with glioblastoma have not benefited from this type of therapy.
“In the last hundred years, there have only been four FDA approved treatments for glioblastoma. We still measure survival in months rather than years, so there is a desperate need to make scientific advances,” said Maciej Lesniak, MD, chair and the Michael J. Marchese Professor of Neurosurgery and senior author of the study.
According to Lesniak, most immunotherapy research has historically focused on T-cells — immune cells that promote adaptive, long-term immunity against viral pathogens and cancer cells. However, previous work regarding B-cells, which support long-term immunity and can also produce antibodies to kill cancer cells, show more promise.
“B-cells can function in many different ways, and certainly can be used a powerful tool to fight cancer by increasing anti-tumor immunity” Lee Chang said.
Putting this to the test, Lee Chang and co-investigators developed a vaccine based on a subpopulation of highly activated B-cells called 41BBL+ B-cells. The team then tested the vaccine in mouse models of glioblastoma, which traveled to lymphoid organs in the mice and promoted the anti-tumor function of CD8T cells, a specialized type of cytotoxic T-cells that attack and kill cancer cells.
Additionally, the B-cells also produced antibodies that bound to the glioblastoma cells, stimulating an immune response and ultimately preventing the growth of new tumors.
“With this vaccine, we are targeting the dual functionality of B-cells to tackle tumor immunosurveillance escape. We aim to utilize both the cellular and humoral immunity of B-cells,” Lee Chang said.
Currently, Lee Chang is collaborating with Northwestern Medicine investigators, including Roger Stupp, MD, the Paul C. Bucy Professor of Neurological Surgery and chief of Neuro-oncology in the Ken and Ruth Davee Department of Neurology, to develop a phase I clinical trial for the vaccine. She said she hopes the vaccine will be able to effectively “awaken” the immune system of glioblastoma patients, which is already severely compromised.
“There is no other vaccine of this kind out there. To have some sort of a footprint in the CD8T cell compartment, once we test this vaccine, will be the real victory,” Lee Chang said.
Lee Chang, Lesniak and Stupp are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
This study was supported by the National Institutes of Health grants P50CA221747, R35CA197725, R01NS093903, R01NS087990, and a National Cancer Institute Specialized Program of Research Excellence (SPORE) grant.
The National Cancer Institute’s five-year SPORE grant supports the advancement of translational research and improve outcomes for patients with brain cancer. The Lurie Cancer Center, one of six programs in the U.S. to have received the competitive grant, is leading a brain cancer SPORE with a special emphasis on glioblastoma.
This article was originally published in the Feinberg School of Medicine News Center on October 7, 2020.
Catalina Lee Chang, PhD, research assistant professor of Neurological Surgery, was the first author of the study published in the Journal of Experimental Medicine.
Maciej Lesniak, MD, chair and the Michael J. Marchese Professor of Neurosurgery, was senior author of the study.
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