Harnessing the body’s B-cells to fight tumors may be a promising treatment for glioblastoma, according to a Northwestern Medicine study recently published in the Journal of Clinical Investigation.
Glioblastoma, one of the most complex and treatment-resistant cancers, has a five-year survival rate of just 6.9 percent, according to the National Brain Tumor Society. The average length of survival is estimated to be around 14-20 months, a figure that has barely improved in decades.
While glioblastoma is notoriously difficult to treat, previous research has shown the promise of a new type of therapy that utilizes the immune system’s own B-cells to target tumors, said Catalina Lee-Chang, PhD, assistant professor of Neurological Surgery and senior author of the new study.
“Our previous work published in the Journal of Experimental Medicine showed a proof-of-concept that we could utilize a very specialized type of B-cells as a therapeutic,” Lee-Chang said. “We really focus on one function of B-cells, which is the activation of CD8 T-cells,” a specialized type of defensive immune cell which are tailored to fight specific pathogens.
In the current study, Lee-Chang and her collaborators set out to test the effectiveness of B-cell vaccines (BVax) and the antibodies they promote to fight glioblastoma tumors.
First, the investigators administered B-cell vaccines to mice with the cancer and conducted immunoproteomics and functional assays. They observed that B-cell vaccines were able to effectively infiltrate the tumor, where B-cells spread out and began producing antibodies.
Through proteomic analyses, investigators found that the B-cell vaccines produced unique antibodies that specifically prevented glioblastoma cell migration and invasion of healthy brains in mice.
Although more research is needed, the findings suggest B-cell vaccines may be a promising strategy for treating glioblastoma, Lee-Chang said.
“The most significant finding here is the confirmation that our B-cell therapies not only can activate tumor-killing CD8 T cells, but a subset of them can infiltrate the tumor and produce therapeutic antibodies,” said Lee-Chang, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “We now have scientific proof that this novel B-cell therapies produce therapeutic antibodies that can inhibit glioblastoma growth.”
Lee-Chang and her collaborators are now working to launch a clinical trial that will study the vaccine’s effectiveness in human glioblastoma patients.
Additionally, B-cell vaccines could be useful in other types of cancer, Lee Chang said.
“This is an autologous B-cell therapy that could be expanded to other indications,” Lee-Chang said. “My lab is already exploring the possibility of using B-cell vaccines to treat other types of solid tumors.”
The study was supported by National Cancer Institute grants R37CA258426, P50CA221747, and Cancer Research Institute grant CR68036. Additional funding was provided by grants from the National Institute of Neurological Diseases, the American Brain Tumor Association, the Cancer Research Institute and the Malnati Brain Tumor Institute.