SynNotch-based activation of NK cells against GBM via TIGIT achieves the local blockade of CD155 and CD73, directly within the GBM TME, thereby mitigating any off-tumor effects and antigen escape, and maximizing the efficacy of targeting GBM-associated checkpoints, by delivering locally-blocking ligands and antibody fragments directly to the GBM-NK cell interface. The gene discussed is PVR; the disease is glioblastoma.