B7-H3 targeted CAR-T cells show highly efficient anti-tumor function against osteosarcoma both in vitro and in vivo

BMC Cancer

卷:22

Research

Guoping Liu¹  Zhiqiang Zhang²  Linsong Zhang³  Yingjiao Pan³  Xingbing Cui³  Qian Zhang³  Zhangjie Gu³  Dehua Li³  Lu Wang³  Xiaoli Tian⁴  Guodi Liu⁵  Ziming Zhang⁶ 

[1] Department of General Surgery, Changhai Hospital, 200433, Shanghai, China;

[2] Department of Pediatric Orthopedics, National Children’s Medical Center & Children’s Hospital of Fudan University, 201102, Shanghai, China;

[3] Shanghai Yihao Biological Technology Co., Ltd, 200231, Shanghai, China;

[4] Shanghai Yihao Biological Technology Co., Ltd, 200231, Shanghai, China;Shanghai Beautiful Life Medical Technology Co., Ltd., 200231, Shanghai, China;

[5] Shanghai Yihao Biological Technology Co., Ltd, 200231, Shanghai, China;State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 200237, Shanghai, China;

[6] Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, 200092, Shanghai, China;Department of Orthopaedics, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, 200062, Shanghai, China;

关键词: Osteosarcoma;    B7-H3;    Chimeric antigen receptor T;    Patient-derived xenografts;   

DOI  :  10.1186/s12885-022-10229-8

 received in 2022-05-04, accepted in 2022-10-25,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundOsteosarcoma (OS) mainly happens in children and youths. Surgery, radiotherapy and chemotherapy are the common therapies for osteosarcoma treatment but all their anti-tumor effects are limited. In recent years, a new cellular therapy, CAR-T, a cellular immunotherapy with genetically engineered T cells bearing chimeric antigen receptor targeting specific tumor-associated antigen, has been proved to be an effective therapy against acute lymphoblastic leukemia. Thus, CAR-T is a potentially effective therapy for osteosarcoma treatment.MethodsA CAR gene targeting B7-H3 antigen was constructed into lentiviral vector through molecular biology techniques. Then, the CAR gene was transferred to T cells through lentiviral delivery system, and the CAR-T cells were largely expanded using in vitro culture technology. The in vitro anti-tumor effect of CAR-T cells was evaluated through Real Time Cell Analysis system (RTCA) and ELISA assay. The in vivo anti-tumor capabilities of CAR-T cells were evaluated using the patient-derived xenografts (PDX) model of osteosarcoma.ResultsThe third-generation CAR-T cells we constructed could target the B7-H3 antigen, and the phenotype of CAR-T cells was consistent with normal T cells; The CAR-T cells showed superior antitumor effects both in vitro and in vivo.ConclusionOur study showed that B7-H3 targeted CAR-T cells had high anti-tumor efficacy against osteosarcoma both in vitro and in vivo, which proved that B7-H3 targeted CAR-T therapy is potentially effective for osteosarcoma treatment.

【 授权许可】

CC BY   
© The Author(s) 2022

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