期刊
ONCOTARGET
卷 8, 期 32, 页码 52866-52876出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17905
关键词
hepatocellular carcinoma; glypican-3; bispecific T cell engager; immunotherapy
资金
- Supporting Programs of the Research Fund of the State Key Laboratory of Oncogenes and Related Genes [91-15-04]
- Program of Shanghai Subject Chief Scientist [16XD1402600]
- National Natural Science Foundation [81502672]
- Shanghai Science and Technology Innovation Action Plan [16DZ1910700]
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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