加拿大麦克马斯特大学Sheila K. Singh团队取得一项新突破。他们的最新研究提出了GPNMB CAR-T细胞对胶质母细胞瘤的双重肿瘤-髓系靶向治疗。相关论文于2026年7月1日发表于国际顶尖学术期刊《自然》杂志上。

在这里，该团队设计了一个多组学靶标发现平台，以确定GPNMB是胶质母细胞瘤中的双室抗原。抗GPNMB CAR-T细胞显示出强大的抗肿瘤活性，在原位患者来源的异种移植物和同基因胶质瘤模型中，通过同时消耗GPNMB+肿瘤和免疫抑制髓细胞群，具有长期的疾病控制作用。通过破坏肿瘤控制和微环境重编程，这些发现提供了抗原选择和靶向异源性、骨髓丰富的实体癌的新策略。

据悉，胶质母细胞瘤是一种致命的脑肿瘤，目前的多种治疗方法很少能防止复发。治疗失败是由广泛的瘤内细胞异质性驱动的，微环境由肿瘤相关巨噬细胞主导，这些巨噬细胞抑制肿瘤生长和免疫抑制。虽然嵌合抗原受体(CAR)-T细胞疗法正在开发用于胶质母细胞瘤，但持续的反应已经被不均匀的抗原表达、抗原丢失和微环境障碍所破坏，而这些不是肿瘤靶向设计直接参与的。这些局限性激发了新的策略，将这种疾病视为肿瘤-免疫系统的耦合，而不是单一的恶性隔间。

附：英文原文

Title: Dual tumour–myeloid targeting of glioblastoma with GPNMB CAR-T cells

Author: Savage, Neil, Grewal, Shan, Shaikh, Muhammad Vaseem, Zemp, Franz J., Mckenna, Dillon, Mikolajewicz, Nicholas, Najem, Hinda, Pyczek, Joanna, Wei, Jiuran, Taleb, Mohamed A. B., Asselstine, Lucas C., Anand, Alisha, Chafe, Shawn C., Zhai, Kui, Maich, William T., Chokshi, Chirayu R., Patel, Hardikkumar, Korman, Tiegan E., Subapanditha, Minomi, Tabunshchyk, Zoya, Tatari, Nazanin, Miletic, Petar, Chen, David, Pacheco, Sebastian, Omar, Abdelsimar T., Wang, Bill, Han, Hong, Chan, Jennifer A., Brown, Kevin R., Venugopal, Chitra, Kislinger, Thomas, Heimberger, Amy B., Moffat, Jason, Mahoney, Douglas J., Singh, Sheila K.

Issue&Volume: 2026-07-01

Abstract: Glioblastoma is a lethal brain tumour for which current multimodal treatment rarely prevents recurrence1. Therapeutic failure is driven by extensive intratumoural cellular heterogeneity2 with a microenvironment dominated by tumour-associated macrophages that sustain tumour growth and immunosuppression3. Although chimeric antigen receptor (CAR)-T cell therapies are being developed for glioblastoma, sustained response has been undermined by non-uniform antigen expression, antigen loss and microenvironmental barriers that are not directly engaged by tumour-targeting designs4. These limitations motivate new strategies that address the disease as a coupled tumour–immune system rather than a single malignant compartment. Here we use a multi-omic target discovery platform to identify GPNMB as a dual-compartment antigen in glioblastoma. Anti-GPNMB CAR-T cells showed potent anti-tumour activity, with long-term disease control in orthotopic patient-derived xenografts and syngeneic glioma models through concomitant depletion of GPNMB+ tumour and immunosuppressive myeloid populations. By collapsing tumour control and microenvironmental reprogramming, these findings provide a new strategy for antigen selection and targeting in heterogenous, myeloid-rich solid cancers.

DOI: 10.1038/s41586-026-10641-1

Source: https://www.nature.com/articles/s41586-026-10641-1

期刊信息

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504

官方网址：http://www.nature.com/

投稿链接：http://www.nature.com/authors/submit_manuscript.html