Open AccessBioactivity and safety of B7‐H3‐targeted chimeric antigen receptor T cells against anaplastic meningioma
Author(s) -
Tang Xin,
Liu Fujun,
Liu Zhiyong,
Cao Yi,
Zhang Zongliang,
Wang Yuelong,
Huang Jianhan,
Fan Shuangming,
Zhao Shasha,
Chen Yaxin,
Li Gaowei,
Wang Shan,
Zheng Meijun,
Hu Yating,
Li Hongjian,
Jiang Caiying,
Yang Meijia,
Yang Hui,
Xu JianGuo,
Guo Gang,
Tong Aiping,
Zhou Liangxue
Publication year - 2020
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1137
Subject(s) - chimeric antigen receptor , antigen , cancer research , meningioma , medicine , infiltration (hvac) , pathology , immunotherapy , immunology , immune system , materials science , composite material
Objective We conducted a first‐in‐human study to evaluate the bioactivity and safety of B7‐H3‐targeted chimeric antigen receptor (CAR) autologous T cells for treating recurrent anaplastic meningioma. Methods Tumor tissues from a patient with recurrent anaplastic meningioma were evaluated for B7‐H3 expression. B7‐H3‐targeted CAR‐T cells were delivered into the intracranial tumor resection cavity using an Ommaya device at a maximum dose of 1.5 × 10 7 cells. Magnetic resonance imaging (MRI) screening and multiple serum indexes were regularly monitored. The patient received surgical intervention after three‐cycle infusions, allowing analysis for CAR‐T‐cell infiltration and target antigen expression in post‐CAR‐T therapy tumor tissues. Results Immunochemical analysis demonstrated high and homogeneous B7‐H3 expression in tumor samples. MRI results indicated that the tumor near the delivery device was relatively stable compared with the rapid progression of tumors distant from the device. We found CAR‐T‐cell trafficking to regions of B7‐H3 + tumor tissues near the device, but not to tumor tissues distant from the device. Decreased B7‐H3 expression was observed near the region of CAR‐T‐cell infiltration after therapy. The intracavitary delivery of B7‐H3‐targeted CAR‐T cells was well‐tolerated and not associated with any toxic effects of grade 3 or higher. Conclusion Our results suggested that although intracavitary administration of B7‐H3‐targeted CAR‐T cells was safe and resulted in local bioactivity, addressing antigen loss and CAR‐T‐cell trafficking may further enhance the applications of B7‐H3‐targeted CAR‐T‐cell therapy.