September 23, 2024
by Olivia Dimmer, Northwestern University
Quantitative analysis of BCR-seq data. Credit: Journal of Clinical Investigation (2024). DOI: 10.1172/JCI177384
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, Ph.D., 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.”
More information: Si Wang et al, B cell-based therapy produces antibodies that inhibit glioblastoma growth, Journal of Clinical Investigation (2024). DOI: 10.1172/JCI177384
Journal information: Journal of Experimental Medicine , Journal of Clinical Investigation
Provided by Northwestern University
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