Team:Fudan/Results

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Results

Antigen density on tumor cells’ surface is heterogeneous. Current cellular immunotherapy only targets cells with high expression of specific tumor antigen. While this approach can improve the precision of recognition, it loses the opportunity to strategically treat tumor cells with different surface antigen densities. We are the first to propose a cellular immunotherapy platform, SwordS (SynNotch-Stripe system), that is capable of generating non-monotonic therapeutic responses to one tumor antigen with different surface densities. We demonstrated our concept with the following experiments. In combining a SynNotch module, which can recognize the antigen, and a Stripe module, which can sort intracellular signal, our engineered cells could generate antigen density dependent tri-response against the target cells with different densities of surface GFP, as well as membrane GPC3 (the tumor antigen of hepatocellular carcinoma). Both experimental data and mathematical simulation show that our platform not only reduces the on-target/off-tumor effects of the original SynNotch system, but also provides a combinational therapeutic solution to treat tumor at various states. We believe that SwordS is a promising platform for the next generation cellular immunotherapy.