Oncotarget

Research Papers:

Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager

Yanyu Bi, Hua Jiang, Peng Wang, Bo Song, Huamao Wang, Xianming Kong and Zonghai Li _

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Oncotarget. 2017; 8:52866-52876. https://doi.org/10.18632/oncotarget.17905

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Abstract

Yanyu Bi1,*, Hua Jiang1,*, Peng Wang2, Bo Song2, Huamao Wang2, Xianming Kong3 and Zonghai Li1,2

1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

2CARsgen Therapeutics, Shanghai, China

3Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

*These authors contributed equally to this work

Correspondence to:

Zonghai Li, email: Zonghaili@shsmu.edu.cn

Xianming Kong, email: kongxianming@renji.com

Keywords: hepatocellular carcinoma, glypican-3, bispecific T cell engager, immunotherapy

Received: January 23, 2017     Accepted: May 04, 2017     Published: May 16, 2017

ABSTRACT

There are limited strategies for the treatment of hepatocellular carcinoma (HCC). In this study, we prepared a Bispecific T cell engager (BiTE) targeting Glypican 3 (GPC3) and CD3. The GPC3/CD3 BiTE was prepared by fusing the single-chain variable fragment (scFv) of the humanized anti-GPC3 antibody (9F2) with the scFv of the anti-CD3 antibody (OKT3). The in vitro and in vivo cytotoxic activities of the GPC3/CD3 BiTE were evaluated against various HCC cell lines. The GPC3/CD3 BiTE could efficiently mediate the T cell killing of GPC3-positive HCC in vitro, which was dependent on GPC3 expression on the surface of HCC cells. Moreover, our study indicates that, in the presence of the GPC3/CD3 BiTE, T cells could efficiently destroy GPC3-positive human HCC cells in vitro and in vivo. Additionally, our study further proved that GPC3 is not expressed in normal tissues. Thus, GPC3 may be a cancer-specific antigen. Collectively, these findings suggest that this anti-GPC3 BiTE might be a promising anti-tumor reagent for patients with GPC3-positive HCC.


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