PDCD1 and neoplasm: Successful multiplex CRISPR-Cas9 editing of CAR T-cells has been done with targeting inhibitory genes (e.g., PDCD1, PD-1) and those encoding death receptors such as CD95/Fas to prevent TME-mediated inhibition or apoptosis [88]. TRAC, PDCD1 and B2M triple knockout CAR T-cells have demonstrated robust anti-tumor function in in vitro and in vivo models incorporating CD19 and prostate stem cell antigen (PSCA)-directed CARs [86, 87].