NK cell-based cancer immunotherapy: from basic biology to clinical development

Liu, Sizhe; Galat, Vasiliy; Galat4, Yekaterina; Lee, Yoo Kyung Annie; Wainwright, Derek; Wu, Jennifer

doi:10.1186/s13045-020-01014-w

Journal of Hematology & Oncology

Table 2 CAR-NK cells that have been evaluated preclinically

From: NK cell-based cancer immunotherapy: from basic biology to clinical development

Target	CAR construct(s)	Source of NK	Method(s)	Cancer type(s)	References
Hematological cancers
CD19	CD19-scFv-CD3ζ, CD19-scFv-CD28-CD3ζ, CD19-scFv-41BB-CD3ζ, CD19-scFv-DAP10-CD3ζ, (iC9).CD19-scFv.CD28-CD3ζ-(IL15)	NK-92, NKL, Cord Blood, peripheral blood	Retrovirus, lentivirus	B cell malignancies	[38, 39, 49, 52, 63]
FLT3	FLT3-scFV-CD28-CD3ζ	NK-92	Lentivirus	B cell acute lymphoblastic leukemia (B-ALL)	[62]
CS1	CS1-scFv-CD28-CD3ζ	NK-92	Lentivirus	Multiple Myeloma	[53]
CD38	Nb(CD38)^a-CD28-41BB-CD3ζ	NK-92 (with CD38 knocked out)	Retrovirus	Multiple Myeloma	[72]
CD4	CD4-scFv-CD28-41BB-CD3ζ	NK-92	Lentivirus	Peripheral T cell lymphoma	[73]
CD5	CD5-scFv-2B4-CD3ζ	NK-92	Lentivirus	T cell malignancies	[46]
CD7	Nb(CD7)-CD28-41BB-CD3ζ	NK-92MI	PiggyBac Transposon System	T cell acute lymphoblastic leukemia (T-ALL)	[67]
Solid cancers
Wild Type EGFR and/or EGFRvIII	EGFR-scFv-CD28-CD3ζ, EGFR-scFv-CD28-41BB-CD3ζ, EGFRvIII-scFv-CD28-CD3ζ, EGFRVIII-scFv-DAP12	NK-92 NKL, YTS	Lentivirus	Glioblastoma, renal cell carcinoma, breast cancer	[47, 51, 58, 59, 71, 76]
ErbB2/HER2	ErbB2-scFv-CD3ζ, ErbB2-scFv-CD28-CD3ζ, ErbB2-scFv-41BB- CD3ζ	NK-92	Lentivirus, Retrovirus	Breast carcinoma, glioblastoma	[48, 60, 70]
GD2	GD2-scFv-CD3ζ	NK-92	Retrovirus	Neuroblastoma, melanoma, breast carcinoma	[65]
Glypican-3 (GPC3)	GPC3-scFv-CD28-41BB-CD3ζ, GPC3-scFv-CD3ζ, GPC3-scFv-CD28-CD3ζ, GPC3-scFv-DNAM1-CD3ζ, GPC3-scFv-DNAM1-2B4-CD3ζ	iPSC, NK-92	Lentivirus	Ovarian cancer, hepatocellular cancer	[57, 66]
EpCAM	EpCAM-scFV-41BB-CD3ζ, EpCAM-scFv-CD28-CD3ζ	NK-92	Lentivirus	Colorectal Cancer	[47, 50, 61]
Mesothelin	Mesothelin-scFv-(NKG2D*)^b-2B4-CD3z, Mesothelin-scFv-CD28-41BB-CD3ζ	NK-92, iPSC	PiggyBac Transposon System; Lentivirus	Ovarian cancer	[42, 75]
Prostate Stem Cell Ag (PSCA)	PSCA-scFv-DAP12	YST cell line, primary NK	Lentivirus	Prostate Cancer	[55]
Carcinoembryonic antigen (CEA)	CEA-scFv-CD3ζ	NK-92MI	Retrovirus	Colorectal Cancer	[69]
CD133	CD133-CD28-41BB-CD3ζ	NK-92	Lentivirus	CD133 + cancer stem cells, ovarian cancer	[64]
c-MET	c-MeT-scFv-41BB–DAP12	Peripheral blood	Lentivirus	Liver cancer	[56]
NKG2D ligands	NKG2D-CD3ζ, NKG2D-CD28- CD3ζ, NKG2D-CD28-41BB-CD3ζ, NKG2D-DAP10-CD3ζ	Peripheral blood, NK-92	RNA electroporation, PiggyBac Transposon System	NKG2DL + cancer cells, Ovarian cancer	[43, 44, 54]
PD-L1	PD1-(NKG2D*)^c-41BB	NK-92	Lentivirus	PD-L1 + tumor cells	[68]
Tissue Factor (TF)	Factor VII light chain (FvIIL)-CD28-41BB-CD3ζ	NK-92MI (transduced to express CD16)	Lentivirus	Triple-negative breast cancer	[74]

For CAR constructs, only the antigen recognition domain and signaling domain(s) are listed unless otherwise specified. Other functional domains will be in parentheses and marked by asterisks (*). Abbreviations: scFv = single-chain variable fragment; FLT3 = FMS-like tyrosine kinase 3;
^aNanobody for CD38
^btransmembrane domain of NKG2D
^chinge region and transmembrane domain of NKG2D

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ISSN: 1756-8722

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