IJMS, Vol. 26, Pages 8941: A Tissue Factor Bi-Specific T-Cell Engager Provides Effective Targeting and Cytotoxicity Against Cervical Cancer Cell Lines

International Journal of Molecular Sciences doi: 10.3390/ijms26188941

Authors:
Kyung-jun Lee
Gilhyang Kim
Booseong Seo
Soo Young Jeong
Hyeong Su Kim
Hye-Yon Cho
Sung Taek Park

Tissue factor (TF), also known as CD142, is a 47 kDa transmembrane glycoprotein belonging to the class II cytokine receptors superfamily. High expression of TF has been reported to be correlated with poor prognosis in various cancers. In this study, we aimed to clarify the cytotoxicity of bi-specific T-cell engagers (BiTE) targeting TF on cervical cancer cell lines. We designed and characterized the novel humanized BiTE targeting TF using an anti-human CD3 single-chain variable fragment (scFv) linked to human TF scFv. TF-Bite replication and potency were assessed in cervical cancer cell lines. The expression of the TF-BiTE and the activation and proliferation of T cells induced along with the T-cell-mediated cytotoxicity were evaluated by flow cytometry in vitro. TF expression was confirmed in SiHa, ME-180, and HeLa cell lines. The TF-BiTE showed potent TF-specific cytotoxicity and induced T-cell activation, proliferation, degranulation, and cytokine release. These effects were not observed in TF-negative control cells. Our findings support TF-BiTE as a promising therapeutic candidate for cervical cancer immunotherapy.

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Kyung-jun Lee www.mdpi.com