How can engineered T-cells be improved with synthetic immunology?

Chimeric antigen receptors (CAR) T cells are T-cells engineered with specific receptor structures that enable them to fight off cancerous cells with more specificity and persistence. Recent research advances this by introducing synthetic notch (synNotch) receptors. These receptors amplify user-defined input and output relationships within cells. This novel receptor allows researchers to program the reduction of on-target off-tumor effects. SynNotch can be part of a dual antigen circuit, where the cell must recognize two antigens to activate and minimize effects on bystander tissues. SynNotch CAR T-cells have been found to reduce T-cell exhaustion compared to traditional CAR T-cells. Another application of synNotch is to express specific cytokines, which are proteins that control the growth and activity of the immune system. This creates a product that assists T-cells with antitumor activity. The various limitations of synNotch include its specified infusion into patients and unpredictable off-target effects. Vaccinations may be another way to utilize synNotch technology in the fight against cancer.