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

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 asse...

Full description

Saved in:
Bibliographic Details
Published in:Translational research : the journal of laboratory and clinical medicine 2023-09, Vol.259, p.1-12
Main Authors: Ji, Feng, Xu, Luxia, Long, Kaili, Zhang, Fan, Zhang, Miaomiao, Lu, Xiao, Xia, Mingyue, Chen, Jiannan, Du, Yu, Tang, Yong, Wu, Heming, Shi, Yan, Ma, Ruiting, Li, Jun, Chen, Zhengliang, Xu, Bin, zhang, Qi, Liang, Junqing, Jia, Shaochang, Hu, Zhigang, Guo, Zhigang
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Glioma - metabolism
Glioma - therapy
Glycoproteins
Humans
Immunotherapy, Adoptive
Mice
Rabies virus
Receptors, Chimeric Antigen
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2023.03.003