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

// Yanyu Bi 1, * , Hua Jiang 1, * , Peng Wang 2 , Bo Song 2 , Huamao Wang 2 , Xianming Kong 3 and Zonghai Li 1, 2 1 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 CARsgen Therapeutics, Shanghai, China 3 Renji 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.