Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma

Authors：Liu, Zhuohao; Zhou, Jiayi; Yang, Xinzhi; Liu, Yuchen; Zou, Chang; Lv, Wen; Chen, Cheng; Cheng, Kenneth King-yip; Chen, Tao; Chang, Lung-Ji^*; Wu, Dinglan^*; Mao, Jie^*

Source：Molecular Cancer, 2023, 22(1): 3.

DOI：10.1186/s12943-022-01711-9

• GD2
• 4SCAR-T
• GBM
• Safety
• Tumor microenvironment

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.

• Institution
  南方医科大学; 1