Fig. 4

Strategies for targeting Notch signaling in cancer immunotherapy. A: Oncolytic virotherapy combined with Notch signaling inhibition. αCD47 can be incorporated into OVs along with gene sequences of antibodies that inhibition of Notch signaling (e.g., αNotch1, αDll1). Also, combination of DAPT, GSI, or other inhibitors of Notch signaling with OVs inhibits the CCL2 secretion of TAMs and the recruitment of MDSCs, and reactivation of CD8⁺ T cells; B: Specific delivery of Notch signaling activators into TAMs. Dll1 ligand and Notch1 overexpression plasmid are packaged into mannose-NPs to specifically target TAMs,  promoting the polarization of TAMs to M1-TAMs and activating CD8⁺ T cells; C: ICBs combined with drugs targeting Notch signaling. D: The synNotch circuit system can be incorporated into CAR immune cells for immunotherapy. Several types of CAR cells can be used to increase anti-tumor capacity. They include synNotch CAR-T cells, synNotch CAR-NK cells, or synNotch CAR-M cells that recognize multiple antigens. These synNotch strategies can enhance the specificity of CAR cells and improve their anti-tumor functions. Figure was created with BioRender.com