B cell–based therapy produces antibodies that inhibit glioblastoma growth

Si Wang(Northwestern University), Brandyn Castro(Northwestern University), Joshua L. Katz(Northwestern University), Víctor A. Arrieta(Northwestern University), Hinda Najem(Northwestern University), Gustavo Vazquez-Cervantes(Northwestern University), Hanxiao Wan(Northwestern University), Ian Olson(Northwestern University), David Hou(Northwestern University), Mark Dapash(Northwestern University), Leah K. Billingham(Northwestern University), Tzu-Yi Chia(Northwestern University), Chao Wei(Northwestern University), Aida Rashidi(Northwestern University), Leonidas C. Platanias(Northwestern University), Kathleen McCortney(Northwestern University), Craig Horbinski(Northwestern University), Roger Stupp(Northwestern University), Peng Zhang(Northwestern University), Atique U. Ahmed(Northwestern University), Adam M. Sonabend(Northwestern University), Amy B. Heimberger(Northwestern University), Maciej S. Lesniak(Northwestern University), Cécile Riviere-Cazaux(Mayo Clinic), Terry C. Burns(Mayo Clinic), Jason Miska(Northwestern University), Mariafausta Fischietti(Northwestern University), Catalina Lee-Chang(Northwestern University)
Journal of Clinical Investigation
August 29, 2024
Cited by 15Open Access
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Abstract

Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options and a poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy is to harness the potential of the immune system against tumor cells. Our previous data showed that the BVax (B cell-based vaccine) can induce therapeutic responses in preclinical models of GBM. In this study, we aimed to characterize the antigenic reactivity of BVax-derived Abs and evaluate their therapeutic potential. We performed immunoproteomics and functional assays in murine models and samples from patients with GBM. Our investigations revealed that BVax distributed throughout the GBM tumor microenvironment and then differentiated into Ab-producing plasmablasts. Proteomics analyses indicated that the Abs produced by BVax had unique reactivity, predominantly targeting factors associated with cell motility and the extracellular matrix. Crucially, these Abs inhibited critical processes such as GBM cell migration and invasion. These findings provide valuable insights into the therapeutic potential of BVax-derived Abs for patients with GBM, pointing toward a novel direction for GBM immunotherapy.


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