(b) Chimeric antigen receptors

Gene	Gene transfer vector	Signaling components	Cell type	Target	Gene transfer efficiency	Ref
CD19	mRNA electroporation	CD3ζ and 4-1BB	Primary NK cells	B cell malignancies	>95% cells	Carlsten et al. [178]
EGFR	Lentivirus	CD3ζ and CD28	NK-92 and NKL	Glioblastoma	N/A	Han et al. [80]
CD19, antimesothelin	Sleeping beauty transposon	CD3ζ, CD28, and 4-1BB	iPSC-derived NK cells	B cell malignancies, ovarian cancer	N/A	Ni et al. [179]
CD19 and IL-15 with iC9 suicide gene	Retrovirus	CD3ζ and CD28	Cord blood NK cells	B cell malignancies	>80%	Liu et al. [66]
ROR1	mRNA electroporation	4-1BB	Peripheral blood NK cells	Neuroblastoma and sarcoma	70% cells	Park et al. [180]
CD22 and CD19-ENG	Retrovirus	CD28 and 4-1BB	Peripheral blood NK cells	B cell malignancies	70–80% of CD22-CARs, and ~50% bispecific CD19-T cell engagers	Velasquez et al. [181]
CD19	VGV-pseudotyped retrovirus	CD28-CD3ζ or CD137-CD3ζ	NK-92	B cell malignancies	N/A	Oelsner et al. [182]
CD123	α-Retroviral SIN	CD28 and 4-1BB	Peripheral blood NK cells	Acute myeloid leukemia	22.9% on day 3; 11.9% on day 9	Klöß et al. [183]
CD20	pLXSN retrovirus	CD3ζ	NK-92	B cell malignancies (in vitro)	93.8–96.3%	Müller et al. [184]
CS1	PCDH lentivirus	CD3ζ and CD28	NK-92 and NKL	Multiple myeloma	>98% (NK-92), >95% (NKL)	Chu et al. [185]
CD4	Lentivirus	CD3ζ, CD28, and 4-1BB	NK-92	T cell lymphoma	>85%	Pinz et al. [186]
PSCA	Self-inactivating pHATtrick lentivirus	CD3ζ, CD28, and DAP12	Peripheral blood NK cells	Prostate cancer stem cells	~50%	Töpfer et al. [74]
NKp44	Retrovirus	CD3ζ and CD28	Peripheral blood NK cells	Enhanced cytotoxicity	N/A	Kasahara et al. [187]
CD19 and HER2	pCCW lentivirus	CD3ζ, CD28, and 4-1BB	NK-92	Solid tumors	N/A	Siegler et al. [188]
CD20	mRNA nucleofection	CD3ζ and 4-1BB	Peripheral blood NK cells	Pediatric Burkitt lymphoma	N/A	Chu et al. [189, 190]
CD138	Lentivirus	CD3ζ (with CD8α)	NK-92MI	Multiple myeloma	>95%	Jiang et al. [130]
ErbB2	Lentivirus	CD3ζ and CD28	NK-92	Glioblastoma	N/A	Steinbach et al. [191]
GD2	pLXSN retrovirus	CD3ζ	NK-92	Neuroblastoma	N/A	Esser et al. [192]
CD33	Electroporation	CD3ζ	YT	Acute myeloid leukemia	90% (after enrichment)	Schirrmann and Pecher [193]
NKG2D	Retrovirus	CD3ζ and DAP10	Peripheral blood NK cells	T-cell ALL, B-cell ALL, osteosarcoma, prostate carcinoma, rhabdomyosarcoma, neuroblastoma, Ewing sarcoma, colon carcinoma, gastric carcinoma, lung squamous cell carcinoma, hepatoma, and breast carcinoma (in vitro), osteosarcoma (in vivo)	80% (range 67–96%)	Chang et al. [194]
EGFR	Lentivirus	CD3ζ and CD28	NK-92	Breast cancer	39.4%	Chen et al. [195]
HER-2	Retrovirus	CD3ζ and CD28	Peripheral blood NK cells	Ovarian and breast cancer cell lines	55 ± 11%	Kruschinski et al. [131]
CD19	Trogocytosis	CD3ζ and 4-1BB	Peripheral blood NK cells	B-ALL cell lines	47% upon coculture with donor cells	Cho et al. [161]
TRAIL-receptor 1	Retrovirus	CD3ζ, 4-1BB, and CD28	KHYG-1	Colo205, Daudi, K562 cells (in vitro)	N/A	Kobayashi et al. [196]
GPC3	Lentivirus	CD8, CD28, and CD3ζ	NK-92 and peripheral blood NK cells	Hepatocellular carcinoma	~35% (primary NK cells)	Yu et al. [197]