机构:[1]State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,[2]Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,[3]Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,[4]Department of Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China,[5]Luogang Chinese Medicine Hospital, Guangzhou, China,[6]Guangdong Zhaotai InVivo Biomedicine Co. Ltd, Guangzhou, China,[7]Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China,[8]Department of Thoracic Oncology, The Second Xiangya Hospital of Central South University, Changcha, China,[9]Department of Hematology, Guangdong Provincial People’s Hospital, Guangzhou, China,[10]Wellcome Trust Sanger Institute, Cambridge, UK
The lack of a general clinic-relevant model for human cancer is a major impediment to the acceleration of novel therapeutic approaches for clinical use. We propose to establish and characterize primary human hepatocellular carcinoma (HCC) xenografts that can be used to evaluate the cytotoxicity of adoptive chimeric antigen receptor (CAR) T cells and accelerate the clinical translation of CAR T cells used in HCC.
Primary HCCs were used to establish the xenografts. The morphology, immunological markers, and gene expression characteristics of xenografts were detected and compared to those of the corresponding primary tumors. CAR T cells were adoptively transplanted into patient-derived xenograft (PDX) models of HCC. The cytotoxicity of CAR T cells in vivo was evaluated.
PDX1, PDX2, and PDX3 were established using primary tumors from three individual HCC patients. All three PDXs maintained original tumor characteristics in their morphology, immunological markers, and gene expression. Tumors in PDX1 grew relatively slower than that in PDX2 and PDX3. Glypican 3 (GPC3)-CAR T cells efficiently suppressed tumor growth in PDX3 and impressively eradicated tumor cells from PDX1 and PDX2, in which GPC3 proteins were highly expressed.
GPC3-CAR T cells were capable of effectively eliminating tumors in PDX model of HCC. Therefore, GPC3-CAR T cell therapy is a promising candidate for HCC treatment.
基金:
This study was supported by the National Natural Science
Foundation of China (NSFC)—81272329, 81522002, 81570156,
and 81327801, Strategic Priority Research Program of the
Chinese Academy of Sciences (XDA01020310), the Natural
Science Fund for Distinguished Young Scholars of Guangdong
Province (2014A030306028), the Guangdong Provincial
Applied Science and Technology Research & Development
Program (2016B020237006), the Guangdong Provincial
Outstanding Young Scholars Award (2014TQ01R068),
the Guangdong Provincial Basic Research Program
(2015B020227003), the Guangdong Provincial Research
and Commercialization Program (2014B090901044), the
Guangdong Province and Chinese Academy of Sciences
Joint Program for Research and Commercialization Program
(2013B091000010), the Guangzhou Basic Research Program
(201510010186), the MOST funding of the State Key
Laboratory of Respiratory Disease, and the National Basic
Research Program of China (973 Program) (2011CB504004
and 2010CB945500), the Frontier and key technology
innovation special grant from the Department of Science
and Technology of Guangdong province (2014B020225005),
and the Guangzhou Science Technology and Innovation
Commission Project (201504010016). Guangzhou Small and
Medium Science and Technology Enterprises Innovation-
Start-Up Project (Grant No: 201605160942469).
第一作者机构:[1]State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,[2]Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,[3]Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,
共同第一作者:
通讯作者:
通讯机构:[1]State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,[2]Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,[3]Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China,
推荐引用方式(GB/T 7714):
Zhiwu Jiang,Xiaofeng Jiang,Suimin Chen,et al.Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carcinoma.[J].FRONTIERS IN IMMUNOLOGY.2017,7:doi:10.3389/fimmu.2016.00690.
APA:
Zhiwu Jiang,Xiaofeng Jiang,Suimin Chen,Yunxin Lai,Xinru Wei...&Peng Li.(2017).Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carcinoma..FRONTIERS IN IMMUNOLOGY,7,
MLA:
Zhiwu Jiang,et al."Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carcinoma.".FRONTIERS IN IMMUNOLOGY 7.(2017)