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Article: Anti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma

TitleAnti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma
Authors
KeywordsCAR
Cell therapy
Hepatocellular carcinoma
PDX
T cells
Issue Date2017
Citation
Frontiers in Immunology, 2017, v. 7, n. JAN How to Cite?
Abstract© 2017 Jiang, Jiang, Chen, Lai, Wei, Li, Lin, Wang, Wu, Liang, Liu, Peng, Yu, Weng, Du, Pei, Liu, Yao, Xue and Li. Background: 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. Methods: 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. Results: 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. Conclusion: 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.
Persistent Identifierhttp://hdl.handle.net/10722/249155
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJiang, Zhiwu-
dc.contributor.authorJiang, Xiaofeng-
dc.contributor.authorChen, Suimin-
dc.contributor.authorLai, Yunxin-
dc.contributor.authorWei, Xinru-
dc.contributor.authorLi, Baiheng-
dc.contributor.authorLin, Simiao-
dc.contributor.authorWang, Suna-
dc.contributor.authorWu, Qiting-
dc.contributor.authorLiang, Qiubin-
dc.contributor.authorLiu, Qifa-
dc.contributor.authorPeng, Muyun-
dc.contributor.authorYu, Fenglei-
dc.contributor.authorWeng, Jianyu-
dc.contributor.authorDu, Xin-
dc.contributor.authorPei, Duanqing-
dc.contributor.authorLiu, Pentao-
dc.contributor.authorYao, Yao-
dc.contributor.authorXue, Ping-
dc.contributor.authorLi, Peng-
dc.date.accessioned2017-10-27T05:59:15Z-
dc.date.available2017-10-27T05:59:15Z-
dc.date.issued2017-
dc.identifier.citationFrontiers in Immunology, 2017, v. 7, n. JAN-
dc.identifier.urihttp://hdl.handle.net/10722/249155-
dc.description.abstract© 2017 Jiang, Jiang, Chen, Lai, Wei, Li, Lin, Wang, Wu, Liang, Liu, Peng, Yu, Weng, Du, Pei, Liu, Yao, Xue and Li. Background: 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. Methods: 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. Results: 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. Conclusion: 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.-
dc.languageeng-
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCAR-
dc.subjectCell therapy-
dc.subjectHepatocellular carcinoma-
dc.subjectPDX-
dc.subjectT cells-
dc.titleAnti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2016.00690-
dc.identifier.scopuseid_2-s2.0-85012070656-
dc.identifier.volume7-
dc.identifier.issueJAN-
dc.identifier.spagenull-
dc.identifier.epagenull-
dc.identifier.eissn1664-3224-
dc.identifier.isiWOS:000391640300001-

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