B cell-based therapy produces antibodies that inhibit glioblastoma growth

作者信息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
PMID39207859
期刊J Clin Invest
发布时间2024-08-29
DOI10.1172/JCI177384

摘要

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.

实验方法

产品清单

名称品牌货号
通用支原体检测试剂盒American Type Culture Collection30-1012K
ImmunoCult人B细胞扩增试剂盒STEMCELL Technologies100-0645
IgG(总)人源非包被ELISA试剂盒Invitrogen88-50550-22
NAb Protein A/G离心柱Thermo Fisher Scientific89962
Protein A/G离心柱----
布拉德福德法试剂盒Bio-Rad500-0006
Thermo Fisher Mem-PER Plus试剂盒Thermo Fisher89842Y
磁性Dynabeads Protein GThermo Fisher Scientific--
BD Symphony流式细胞分析仪BD--
4× Laemmli上样缓冲液Bio-Rad--
TRIzol试剂Invitrogen--
ImmunoSEQ平台Adaptive Biotechnologies--
Lunaphore COMET平台Lunaphore--
多重染色缓冲液Lunaphore TechnologiesBU06
洗脱缓冲液Lunaphore TechnologiesBU07-L
淬灭缓冲液Lunaphore TechnologiesBU08-L
成像缓冲液Lunaphore TechnologiesBU09
M Dialysis 71高截留分子量脑微透析导管M Dialysis--
107微透析泵----
带确定无细胞间隙的硅胶插件IBIDI80206
康宁Matrigel侵袭小室Corning354480
CellTiter-Glo 2.0细胞活力检测试剂盒PromegaG9242
徕卡显微镜Leica--
汉密尔顿注射器----