Safety and Antitumor Activity of GD2-Specific 4SCAR-T Cells in Patients with Glioblastoma

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2023 Jan 8

PMID 36617554

Authors

Zhuohao Liu

Jiayi Zhou

Xinzhi Yang

Yuchen Liu

Chang Zou

Wen Lv

Cheng Chen

Kenneth King-Yip Cheng

Tao Chen

Lung-Ji Chang

Dinglan Wu

Jie Mao

Affiliations

Soon will be listed here.

Abstract

Background: This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity.

Methods: A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration.

Results: 4SCAR-T cells expanded for 1-3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion.

Conclusion: Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted.

Trial Registration: ClinicalTrials.gov Identifier: NCT03170141 . Registered 30 May 2017.

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