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B cell–based therapy produces antibodies that inhibit glioblastoma growth
Si Wang, … , Mariafausta Fischietti, Catalina Lee-Chang
Si Wang, … , Mariafausta Fischietti, Catalina Lee-Chang
Published August 29, 2024
Citation Information: J Clin Invest. 2024;134(20):e177384. https://doi.org/10.1172/JCI177384.
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Research Article Immunology Oncology

B cell–based therapy produces antibodies that inhibit glioblastoma growth

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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.

Authors

Si Wang, Brandyn A. Castro, Joshua L. Katz, Victor Arrieta, Hinda Najem, Gustavo I. Vazquez-Cervantes, Hanxiao Wan, Ian E. Olson, David Hou, Mark Dapash, Leah K. Billingham, Tzu-yi Chia, Chao Wei, Aida Rashidi, Leonidas C. Platanias, Kathleen McCortney, Craig M. Horbinski, Roger Stupp, Peng Zhang, Atique U. Ahmed, Adam M. Sonabend, Amy B. Heimberger, Maciej S. Lesniak, Cécile Riviere-Cazaux, Terry Burns, Jason Miska, Mariafausta Fischietti, Catalina Lee-Chang

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Figure 1

BVax differentiates into plasmablasts and generates potentially tumor-reactive B cell Igs.

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BVax differentiates into plasmablasts and generates potentially tumor-re...
(A) Schema illustrating the experimental design to investigate the potential of BVax to migrate to the glioma and differentiate into Ab-producing cells (plasmablasts). i.c., intracranial; T, tumor; NT, nontumor. (B) Percentage of BVax (CD45.1+) cells in various tissues (blood, brain, deep cervical lymph node [dCLN], and spleen) of intracranial tumor–bearing and nontumor-bearing mice via flow cytometry (n = 5 for each group). (C) GSEA of the indicated datasets comparing the transcriptional profile between BVax and BNaive. Data were pooled from 3 independent experiments. (D) Percentage of plasmablasts (CD19+CD20–CD38+) within the BVax population of the brain via flow cytometry (n = 8 for each group). (E) Representative dot plot of BCR clones from BCR IgH sequencing comparing murine BVax and BNaive. Unique clones in BVax are shown in red; unique clones in BNaive are shown in blue (n = 3 for each group). (F) Representative dot plot of BCR clones from BCR IgH sequencing comparing murine TIB cells (n = 2) and BVax (n = 3). Unique clones in TIB cells are shown in red; unique clones in BVax are shown in blue. Data are the mean ± SD. ***P < 0.001 and ****P < 0.0001, by 1-way ANOVA. NT, nontumor; T, tumor.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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