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

Liu, Zhuohao1,2,3,4; Zhou, Jiayi2,3; Yang, Xinzhi1,3,4; Liu, Yuchen5; Zou, Chang6; Lv, Wen4; Chen, Cheng4; Cheng, Kenneth King-yip7; Chen, Tao2,3; Chang, Lung-Ji5; Wu, Dinglan2,3; Mao, Jie4

2023-01-09

10.1186/s12943-022-01711-9

MOLECULAR CANCER   Impact Factor & Quartile

1476-4598

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.

GD2 4SCAR-T GBM Safety Tumor microenvironment

SCI

English

Corresponding

Young Scientists Fund of the National Natural Science Foundation of China (NSFC)[81900801] ; NSFC[8227161245] ; Shenzhen Basic Research Program of Shenzhen Science and Technology Innovation Commission["JCYJ20220530152614033","JCYJ20180508163203807","JCYJ20190814114403618","RCBS20200714114909325"]

Biochemistry & Molecular Biology ; Oncology

Biochemistry & Molecular Biology ; Oncology

WOS:000910981800001

BMC

Web of Science

1.Southern Med Univ, Shenzhen Hosp, Dept Neurosurg, Shenzhen, Guangdong, Peoples R China
2.Southern Med Univ, Shenzhen Hosp, Clin Innovat & Res Ctr, Shenzhen Key Lab Viral Oncol, Shenzhen, Guangdong, Peoples R China
3.Southern Med Univ, Sch Clin Med 3, Shenzhen, Guangdong, Peoples R China
4.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China
5.Shenzhen Geno Immune Med Inst, Shenzhen, Guangdong, Peoples R China
6.Chinese Univ Hong Kong Shenzhen, Sch Med Life & Hlth Sci, Shenzhen, Guangdong, Peoples R China
7.Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Peoples R China

Liu, Zhuohao,Zhou, Jiayi,Yang, Xinzhi,et al. Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma[J]. MOLECULAR CANCER,2023,22(1).

Liu, Zhuohao.,Zhou, Jiayi.,Yang, Xinzhi.,Liu, Yuchen.,Zou, Chang.,...&Mao, Jie.(2023).Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma.MOLECULAR CANCER,22(1).

Liu, Zhuohao,et al."Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma".MOLECULAR CANCER 22.1(2023).