Development of CAR-NK cell therapies in the industry. (A) GoCAR-NK utilizes Rimiducid and Rapamycin for inducible activation and suicide signaling, respectively. (B) FT596, combined with Rituximab, can target both CD19 and CD20 with CD16 Fc receptor in B cell malignancy. IL-15 receptor fusion protein with a flexible IL-15 is introduced for further NK cell activation. (C) ONK therapeutics use TRAIL signaling for maximizing tumor cell apoptosis. A high-affinity variant of TRAIL is recognized by the DR5 TRAIL receptor, thereby resulting in activation of FADD-Caspase8 signaling in a target tumor cell. (D) t-haNK is a versatile platform targeting tumors with a combination of CAR and therapeutic antibody. In this figure, we illustrate an example of NSCLC which expresses a high level of PD-L1 and EGFR. ER-retained IL-2 also drives NK cell activation and persistence. (E) NKX-101 uses NKG2D-CAR for tumor antigen recognition, membrane-bound IL-15 for further activation as well. NKG2D ligands (MIC and RAET1 families) are highly expressed in various tumor cells.
