Anti-tumor efficacy of anti-GD2 CAR NK-92 cells in diffuse intrinsic pontine gliomas

Frontiers in Immunology

Immunology

Pengcheng Zuo¹  Zhen Wu¹  Junting Zhang¹  Liwei Zhang²  Tantan Wang³  Yaopeng Li³  Chi He³  Hao Liu³  Xuebin Liao⁴  Xu Zheng⁵ 

[1] Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China;School of Pharmaceutical Sciences, Peking-Tsinghua Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing, China;School of Pharmaceutical Sciences, Peking-Tsinghua Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing, China;Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;Yufan Biotechnology (Beijing) Co., LTD, Beijing, China;

关键词: GD2;    CARNK;    anti-tumor efficacy;    diffuse intrinsic pontine gliomas;    pediatric;   

DOI  :  10.3389/fimmu.2023.1145706

 received in 2023-01-16, accepted in 2023-04-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundDiffuse intrinsic pontine gliomas (DIPGs) are rare and fatal pediatric brainstem gliomas with no cure. Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have been proven effective in treating glioblastoma (GBM) in preclinical studies. However, there are no relevant studies on the CAR-NK treatment for DIPG. Our study is the first to evaluate the anti-tumor activity and safety of GD2-CAR NK-92 cells treatment for DIPG.MethodsFive patient-derived DIPG cells and primary pontine neural progenitor cell (PPC) were used to access disialoganglioside GD2 expression. Cell killing activity of GD2-CAR NK-92 cells was analyzed by in vitro cytotoxicity assays. Two DIPG patient-derived xenograft models were established to detect the anti-tumor efficacy of GD2-CAR NK-92 cells in vivo.ResultsAmong the five patient-derived DIPG cells, four had high GD2 expression, and one had low GD2 expression. In in vitro assays, GD2-CAR NK-92 cells could effectively kill DIPG cells with high GD2 expression while having limited activity against DIPG cells with low GD2 expression. In in vivo assays, GD2-CAR NK-92 cells could inhibit tumor growth in TT150630 DIPG patient-derived xenograft mice (high GD2 expression) and prolong the overall survival of the mice. However, GD2-CAR NK-92 showed limited anti-tumor activity for TT190326DIPG patient-derived xenograft mice (low GD2 expression).ConclusionOur study demonstrates the potential and safety of GD2-CAR NK-92 cells for adoptive immunotherapy of DIPG. The safety and anti-tumor effect of this therapy need to be further demonstrated in future clinical trials.

【 授权许可】

Unknown   
Copyright © 2023 Zuo, Li, He, Wang, Zheng, Liu, Wu, Zhang, Liao and Zhang