Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Department of Neurological Surgery, Loyola University Chicago Stritch School of Medicine, Chicago, IL.
J Exp Med. 2021 Jan 4;218(1). doi: 10.1084/jem.20200913.
Immunotherapy has revolutionized the treatment of many tumors. However, most glioblastoma (GBM) patients have not, so far, benefited from such successes. With the goal of exploring ways to boost anti-GBM immunity, we developed a B cell-based vaccine (BVax) that consists of 4-1BBL+ B cells activated with CD40 agonism and IFNγ stimulation. BVax migrates to key secondary lymphoid organs and is proficient at antigen cross-presentation, which promotes both the survival and the functionality of CD8+ T cells. A combination of radiation, BVax, and PD-L1 blockade conferred tumor eradication in 80% of treated tumor-bearing animals. This treatment elicited immunological memory that prevented the growth of new tumors upon subsequent reinjection in cured mice. GBM patient-derived BVax was successful in activating autologous CD8+ T cells; these T cells showed a strong ability to kill autologous glioma cells. Our study provides an efficient alternative to current immunotherapeutic approaches that can be readily translated to the clinic.
免疫疗法已经彻底改变了许多肿瘤的治疗方法。然而，到目前为止，大多数胶质母细胞瘤（GBM）患者并未从中受益。为了探索增强抗 GBM 免疫的方法，我们开发了一种基于 B 细胞的疫苗（BVax），该疫苗由用 CD40 激动剂和 IFNγ 刺激激活的 4-1BBL+B 细胞组成。BVax 迁移到关键的次级淋巴器官，并擅长抗原交叉呈递，这促进了 CD8+T 细胞的存活和功能。放射治疗、BVax 和 PD-L1 阻断的联合治疗在 80%的接受治疗的荷瘤动物中实现了肿瘤消除。这种治疗引发了免疫记忆，防止了在治愈小鼠中再次注射新肿瘤的生长。GBM 患者来源的 BVax 成功地激活了自体 CD8+T 细胞；这些 T 细胞显示出强烈的杀伤自体神经胶质瘤细胞的能力。我们的研究为当前的免疫治疗方法提供了一种有效的替代方案，并且可以很容易地转化为临床应用。
