2. Academic Validation
  3. Rabies virus glycoprotein 29 (RVG29) promotes CAR-T immunotherapy for glioma

Rabies virus glycoprotein 29 (RVG29) promotes CAR-T immunotherapy for glioma

  • Transl Res. 2023 Sep:259:1-12. doi: 10.1016/j.trsl.2023.03.003.
Feng Ji 1,  Luxia Xu 2,  Kaili Long 2,  Fan Zhang 2,  Miaomiao Zhang 2,  Xiao Lu 3,  Mingyue Xia 2,  Jiannan Chen 2,  Yu Du 2,  Yong Tang 4,  Heming Wu 4,  Yan Shi 4,  Ruiting Ma 2,  Jun Li 2,  Zhengliang Chen 2,  Bin Xu 5,  Qi Zhang 5,  Junqing Liang 6,  Shaochang Jia 7,  Zhigang Hu 8,  Zhigang Guo 9
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China; Zhongda Hospital, Southeast University, Nanjing, China. Electronic address: fengjii@foxmail.com.
  • 2 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
  • 3 Xiamen University, Xiamen, China.
  • 4 Nanjing First Hospital, Nanjing, China.
  • 5 Zhongda Hospital, Southeast University, Nanjing, China.
  • 6 The Affiliated People's Hospital of Inner Mongolia Medical University, Inner Mongolia, China.
  • 7 Jinling Hospital of Nanjing University, Nanjing, China.
  • 8 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China. Electronic address: huzg_2000@126.com.
  • 9 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China. Electronic address: guo@njnu.edu.cn.
PMID: 36977441 DOI: 10.1016/j.trsl.2023.03.003
Abstract

Chimeric antigen receptor T cell (CAR-T) therapy has limited efficacy for treating glioma because of the infiltrative nature of the blood-brain barrier (BBB) and T cell exhaustion. Conjugation with rabies virus glycoprotein (RVG) 29 enhances the brain-related efficacy of various agents. Here we assess whether RVG enhances the ability of CAR-T cells to cross the BBB and improves their immunotherapy. We generated 70R CAR-T cells (anti-CD70 CAR-T modified with RVG29) and validated their tumor-killing efficacy in vitro and in vivo. We validated their effects on tumor regression in a human glioma mouse orthotopic xenograft model as well as in patient-derived orthotopic xenograft (PDOX) models. The signaling pathways activated in 70R CAR-T cells were revealed by RNA Sequencing. The 70R CAR-T cells we generated showed effective antitumor function against CD70+ glioma cells both in vitro and in vivo. 70R CAR-T cells were better able to cross the BBB into the brain than CD70 CAR-T cells under the same treatment conditions. Moreover, 70R CAR-T cells significantly promote the regression of glioma xenografts and improve the physical characteristics of mice without causing overt adverse effects. RVG modification enables CAR-T cells to cross the BBB, and stimulation with glioma cells induces 70R CAR-T cells to expand in a resting state. The modification of RVG29 has a positive impact on CAR-T therapy for brain tumors and may have potential in CAR-T therapy for glioma.

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