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

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 8

BVax cells from tumor-bearing mice have a superior ability to produce Abs that localize to the peritumoral region and promote survival of GBM-bearing mice survival.

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BVax cells from tumor-bearing mice have a superior ability to produce Ab...
(A) Representative images of H&E and IF staining for anti–mouse IgG and IgM to assess the presence and localization of BVax-derived Igs. BVax or BNaive cells from healthy or CT2A tumor–bearing C57BL/6 mice were adoptively transferred into CT2A tumor–bearing muMT mice. Following treatment, brain tissues were harvested from recipient mice and stained for anti–mouse IgG and IgM (red). H&E-stained images show the organization of the tumors and the locations where the IF images were taken: peritumoral region (dotted green line), intratumoral region (orange box), and relatively normal brain (purple box). (B) Quantification of the relative intensity of BVax-Igs in the peritumoral region. A total of 10–15 images were taken around the peritumoral region in each mouse (dotted green line). The MFI of anti–mouse IgG and IgM (red) in each image was quantified using ImageJ as described previously (68, 69). PBS group: n = 3; BVaxCT2A group: n = 5; BNaiveCT2A group: n = 5; BVaxhealthy group: n = 3; BNaivehealthy group: n = 3. Data are representative of 2 independent experiments. (C) Quantification of satellites (black arrowhead) away from the CT2A tumor core based on H&E images from each mouse. PBS group: n = 3; BVax-CT2A group: n = 5; BNaiveCT2A group: n = 5; BVax healthy group: n = 3; BNaivehealthy group: n = 3. The data are representative of 2 independent experiments. (D) Survival of CT2A tumor–bearing mice was evaluated in 3 groups: mock-treated (n = 8), BNaive Ig–treated (n = 9), and BVax Ig–treated (n = 10). (E) Survival of CT2A tumor–bearing muMT mice was assessed according to the 3 treatment groups: PBS control (n = 5), WT BVax (n = 6), and Prdm1-deficient BVax (n = 6). Data are presented as the mean ± SD. **P < 0.01, ***P < 0.001, and ****P < 0.0001, by 1-way ANOVA (B and C) or log-rank test (D and E).