B cell–based therapy produces antibodies that inhibit glioblastoma growth
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
- Kathleen McCortney (ORCID: https://orcid.org/0000-0001-7085-830X)
- Terry C. Burns (ORCID: https://orcid.org/0000-0001-7633-3045)
- David Hou (ORCID: https://orcid.org/0000-0002-1224-0146)
- Hinda Najem (ORCID: https://orcid.org/0000-0003-4432-9708)
- Atique U. Ahmed (ORCID: https://orcid.org/0000-0003-4795-0188)
- Craig Horbinski (ORCID: https://orcid.org/0000-0001-8340-9992)
- Aida Rashidi (ORCID: https://orcid.org/0000-0002-4555-1514)
- Gustavo Vazquez-Cervantes
- Mark Dapash (ORCID: https://orcid.org/0000-0002-8695-2373)
- Víctor A. Arrieta (ORCID: https://orcid.org/0000-0003-2738-9741)
- Ian Olson (ORCID: https://orcid.org/0000-0001-6692-4538)
- Joshua L. Katz (ORCID: https://orcid.org/0000-0003-4133-5731)
- Brandyn Castro (ORCID: https://orcid.org/0000-0003-3412-9761)
- Cécile Riviere-Cazaux (ORCID: https://orcid.org/0000-0002-8857-4345)
- Leah K. Billingham
- Catalina Lee-Chang (ORCID: https://orcid.org/0000-0002-7675-2124)
- Tzu-Yi Chia
- Leonidas C. Platanias (ORCID: https://orcid.org/0000-0002-9740-7573)
- Roger Stupp (ORCID: https://orcid.org/0000-0002-5483-3118)
- Hanxiao Wan
- Mariafausta Fischietti
- Maciej S. Lesniak (ORCID: https://orcid.org/0000-0002-0096-5107)
- Adam M. Sonabend (ORCID: https://orcid.org/0000-0002-8347-1945)
- Chao Wei (ORCID: https://orcid.org/0000-0002-7425-5132)
- Jason Miska (ORCID: https://orcid.org/0000-0001-9608-2810)
- Amy B. Heimberger (ORCID: https://orcid.org/0000-0002-9970-8695)
- Peng Zhang (ORCID: https://orcid.org/0000-0003-1771-7545)
- Si Wang (ORCID: https://orcid.org/0000-0003-2431-0612)
Institutions
- Northwestern University (US)
- Allen Institute for Brain Science (US)
- Mayo Clinic (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- Jesse Brown VA Medical Center (US)
- Mayo Clinic in Florida (US)
- Neurological Surgery (US)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1172/jci177384
- Citations
- 14
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- National Institutes of Health