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B cell-based therapy produces antibodies that inhibit glioblastoma growth

Authors :
Wang, Si
Castro, Brandyn A.
Katz, Joshua L.
Arrieta, Victor
Najem, Hinda
Vazquez-Cervantes, Gustavo I.
Wan, Hanxiao
Olson, Ian E.
Hou, David
Dapash, Mark
Billingham, Leah K.
Chia, Tzu- yi
Wei, Chao
Rashidi, Aida
Platanias, Leonidas C.
McCortney, Kathleen
Horbinski, Craig M.
Stupp, Roger
Zhang, Peng
Ahmed, Atique U.
Sonabend, Adam M.
Heimberger, Amy B.
Lesniak, Maciej S.
Riviere-Cazaux, Cecile
Burns, Terry
Miska, Jason
Fischietti, Mariafausta
Lee-Chang, Catalina
Source :
Journal of Clinical Investigation. October 15, 2024, Vol. 134 Issue 20
Publication Year :
2024

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 [B.sub.Vax] (B cell- based vaccine) can induce therapeutic responses in preclinical models of GBM. In this study, we aimed to characterize the antigenic reactivity of [B.sub.Vax]-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 [B.sub.Vax] distributed throughout the GBM tumor microenvironment and then differentiated into Ab-producing plasmablasts. Proteomics analyses indicated that the Abs produced by [B.sub.Vax] 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 [B.sub.Vax]-derived Abs for patients with GBM, pointing toward a novel direction for GBM immunotherapy.<br />Introduction Glioblastoma (GBM) is an aggressive and malignant brain tumor that arises from glial cells (1). GBM is one of the most common and deadly forms of brain cancer in [...]

Details

Language :
English
ISSN :
00219738
Volume :
134
Issue :
20
Database :
Gale General OneFile
Journal :
Journal of Clinical Investigation
Publication Type :
Academic Journal
Accession number :
edsgcl.815927170
Full Text :
https://doi.org/10.1172/JCI177384