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ResearchIn-Press PreviewImmunologyOncology Open Access | 10.1172/JCI177384

B cell-based therapy produces antibodies that inhibit glioblastoma growth

Si Wang,1 Brandyn A. Castro,1 Joshua L. Katz,1 Victor A. Arrieta,1 Hinda Najem,1 Gustavo I. Vazquez-Cervantes,1 Hanxiao Wan,1 Ian E. Olson,1 David Hou,1 Mark Dapash,1 Leah K. Billingham,1 Tzu-Yi Chia,1 Chao Wei,1 Aida Rashidi,1 Leonidas C. Platanias,2 Kathleen McCortney,1 Craig M. Horbinski,1 Roger Stupp,1 Peng Zhang,1 Atique U. Ahmed,1 Adam M. Sonabend,1 Amy B. Heimberger,1 Maciej S. Lesniak,3 Cecile Riviere-Cazaux,4 Terry C. Burns,5 Jason Miska,1 Mariafausta Fischietti,2 and Catalina Lee-Chang1

1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, United States of America

3Neurological Surgery, Northwestern University, Chicago, United States of America

4Department of Neurological Surgery, Mayo Clinic, Rochester, United States of America

5Department of Neurological Surgery, Mayo Cinic, Rochester, United States of America

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Published August 29, 2024 - More info

J Clin Invest. https://doi.org/10.1172/JCI177384.
Copyright © 2024, Wang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 29, 2024 - Version history
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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 aim to characterize the antigenic reactivity of BVax-derived antibodies and evaluate their therapeutic potential. We performed immunoproteomics and functional assays in murine models and human GBM patient samples. Our investigations revealed that BVax distributes throughout the GBM tumor microenvironment (TME) and then differentiates into antibody-producing plasmablasts. Proteomic analyses indicate that the antibodies produced by BVax display unique reactivity, predominantly targeting factors associated with cell motility and the extracellular matrix. Crucially, these antibodies inhibit critical processes such as GBM cell migration and invasion. These findings provide valuable insights into the therapeutic potential of BVax-derived antibodies for GBM patients, pointing towards a novel direction in GBM immunotherapy.

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  • Version 1 (August 29, 2024): In-Press Preview
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