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• W4303946581 abstract "Bi-specific T cell engager (BiTE), an artificial bi-functional fusion protein, has shown promising therapeutic potential in preclinical and clinical studies. However, T cells cannot be sufficiently activated by BiTE, most likely due to lacking co-stimulatory signal. We reasoned that incorporating co-stimulatory signal might have the potential to enhance the T cell activation mediated by BiTE. We, therefore, designed a chimeric fusion protein, named as CD3εζ28, which consists of the CD3ε extracellular region, the CD28 costimulatory signal and the intracellular region of CD3ζ in tandem. T cells genetically modified to express both CD3εζ28 and GFP (T-CD3εζ28-GFP) were generated by retroviral transduction. The results from in vitro experiments showed that T-CD3εζCD28-GFP cells had superior cytotoxic effects on tumor cells in presence of BiTE compared with control T cells, as evidenced by IL-2 and IFN-γ production, T cell proliferation and sequential killing assay. In vivo, T-CD3εζCD28-GFP cells showed superior anti-tumor effects in Hela-BiTE. EGFRvIII xenograft tumor model, as evaluated by tumor growth rate and T cell persistence in comparison with control T cells. In order to further confirm these findings, we generated T cells modified to express both CD3εζCD28 on cell surface and BiTE.CD19 by autocrine manner (T-CD3εζCD28-BiTE.19). The superior anti-tumor effects of T-CD3εζCD28-BiTE.19 cells could also be evidenced by the similar in vitro and in vivo experiments; thus, incorporating co-stimulatory signal may be an effective approach to improve the effector function of T cells mediated by BiTE." @default.
• W4303946581 created "2022-10-10" @default.
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• W4303946581 date "2022-10-09" @default.
• W4303946581 modified "2023-09-25" @default.
• W4303946581 title "Combination of a Novel Fusion Protein CD3εζ28 and Bispecific T Cell Engager Enhances the Persistance and Anti-Cancer Effects of T Cells" @default.
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• W4303946581 doi "https://doi.org/10.3390/cancers14194947" @default.
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