B cell-based therapy produces antibodies that inhibit glioblastoma growth.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Journal of Clinical Investigation Pub Date : 2024-08-29 DOI:10.1172/JCI177384
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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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.

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基于 B 细胞的疗法能产生抑制胶质母细胞瘤生长的抗体。
胶质母细胞瘤(GBM)是一种侵袭性极强的恶性脑肿瘤,治疗手段有限,预后较差。尽管目前有多种治疗方法,但 GBM 的侵袭性往往导致复发。利用免疫系统的潜力来对抗肿瘤细胞是一种很有前景的替代策略。我们之前的数据显示,Bvax(基于 B 细胞的疫苗)可以在 GBM 临床前模型中诱导治疗反应。在本研究中,我们旨在描述 BVax 衍生抗体的抗原反应性并评估其治疗潜力。我们在小鼠模型和人类 GBM 患者样本中进行了免疫蛋白组学和功能测定。我们的研究发现,BVax分布在整个GBM肿瘤微环境(TME)中,然后分化成产生抗体的浆细胞。蛋白质组分析表明,BVax 产生的抗体具有独特的反应性,主要靶向与细胞运动和细胞外基质相关的因子。最重要的是,这些抗体能抑制 GBM 细胞迁移和侵袭等关键过程。这些发现为 BVax 衍生抗体对 GBM 患者的治疗潜力提供了宝贵的见解,为 GBM 免疫疗法指明了新的方向。
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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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