Fig. 4

Overview of engineered NK cell therapies. From left to right: different NK cell sources (PB-NK, UCB-NK, HSC-derived NK, iPSC-derived NK, NK-92) are engineered to express the desired surface protein(s) by means of non-viral electroporation with mRNA (left) or of transduction with γ-retro or lentiviral vectors and stable integration in the host genome (right). Engineered NK cell therapies can be divided in categories, according to the targeting molecule: (1) antibody-derived single-chain variable fragment (scFv-engineered) for tumor antigen binding, (2) NK cell receptor (receptor-engineered) for ligand binding, and (3) Fc receptor CD16 (158 V) high-affinity non-cleavable hnCD16 variant (CD16-engineered) to enhance antibody-dependent cell cytotoxicity (ADCC). Co-expression of scFv and hnCD16 is also reported. Additional modifications of engineered NK cell products under clinical evaluation enhance NK cell persistence in vivo by expression of membrane-bound IL-15 or of IL-15/IL-15 receptor fusion protein IL-15/IL-15Ra, prevent fratricide by CD38 KO, or increase safety through induction of apoptosis by administration of Rimiducid