Renaissance of armored immune effector cells, CAR-NK cells, brings the higher hope for successful cancer therapy

Marofi, Faroogh; Rahman, Heshu Sulaiman; Thangavelu, Lakshmi; Dorofeev, Aleksey; Bayas-Morejón, Favian; Shirafkan, Naghmeh; Shomali, Navid; Chartrand, Max Stanley; Jarahian, Mostafa; Vahedi, Ghasem; Mohammed, Rebar N.; Shahrokh, Somayeh; Akbari, Morteza; Khiavi, Farhad Motavalli

doi:10.1186/s13287-021-02251-7

Stem Cell Research & Therapy

Table 1 Preclinical trials of CAR-engineered NK cells

From: Renaissance of armored immune effector cells, CAR-NK cells, brings the higher hope for successful cancer therapy

Hematological malignancies
Target	Malignancy	Signaling domain	Source of NK cells	Genetic modification method	Reference
CD19	B cell acute lymphoblastic leukemia (B-ALL)/B cell malignancies	CD28 + CD3ζ	Primary human NK cells from PBMCs	Lentiviral transduction	[168]
CD19	B cell acute lymphoblastic leukemia (B-ALL)/B cell malignancies	2B4 + CD3ζ	Primary human NK cells from PBMCs	retroviral transduction	[165]
CD19	B cell acute lymphoblastic leukemia (B-ALL)/B cell malignancies	4-1BB + CD3ζ	Primary human NK cells from PBMCs	mRNA electroporation	[128]
CD19	(B-ALL) and non-Hodgkin lymphoma (NHL)/B cell malignancies	4-1BB + CD3ζ	Primary human NK cells from PBMCs	mRNA electroporation; retroviral transduction	[129]
CD19	B-ALL cells/ B cell malignancies	4-1BB/CD3ζ	Primary human NK cells from PBMCs	Trogocytosis	[134]
CD19	B cell malignancies	CD3ζ	UCB	Retroviral transduction	[55]
CD19	B cell malignancies	CD3ζ	NK-92 cells	Retroviral transduction	[76]
CD19	CLL/ B cell malignancies	CD3ζ	NK-92 cells	mRNA electroporation	[75]
CD19	B cell malignancies	CD3ζ CD28 + CD3ζ 4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[169]
CD19	CD20 resistant non-Hodgkin lymphoma (bNHL)	CD28 + CD3ζ	NK-92 cells	NR	[141]
CD20	B cell malignancies non–Hodgkin lymphoma (bNHL)	4-1BB + CD3ζ	Primary human NK cells from PBMCs	mRNA electroporation	[170]
CD20	B cell malignancies	CD3ζ	NK-92 cells	Retroviral transduction	[140]
CD19 and CD20	B cell malignancies	CD3ζ	NK-92 cells	Lentiviral transduction	[171]
CS1	Multiple myeloma	CD28 + CD3ζ	NK-92 cells	Lentiviral transduction	[145]
CD138	Multiple myeloma	CD3ζ	NK-92MI cells	Lentiviral transduction	[146]
FLT3	B-ALL/B cell malignancies	CD28 + CD3ζ	NK-92 cells	Lentiviral transduction	[142]
CD5	T cell malignancies	CD28 + 4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[73]
CD5	T cell malignancies	CD28 + CD3ζ	NK-92 cells	Lentiviral transduction	[172]
CD3	T cell malignancies	CD28 + 4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[98]
CD4	T cell malignancies	CD28 + 4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[143]
EBNA3C	EBV-positive T cells	4-1BB + CD3ζ	NK-92MI cells	Retroviral transduction	[173]
Solid tumors
GD2	Ewing sarcoma	CD28 + 4-1BB + CD3ζ	Primary human NK cells from PBMCs	Retroviral transduction	[167]
GD2	Neuroblastoma	CD3ζ	NK-92 cells	Retroviral transduction	[166]
GD2	Neuroblastoma	2B4 + CD3ζ	Primary NK cells from PBMC and NK-92 cells	Retroviral transduction	[165]
EpCAM	Breast cancer	CD28 + CD3ζ	NK-92 and NKL cells	Lentiviral transduction	[174]
EpCAM	Colorectal cancer	4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[162]
Carbonic Anhydrase IX (CAIX)	Renal cell carcinoma (RCC)	CD28 + 4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[175]
PSCA	Prostate cancer/PSCA⁺ tumor cells	DAP12	Primary human NK cells from PBMCs and YTS cells	Lentiviral transduction	[80]
GPA7	Melanoma	CD3ζ	NK-92 cells	mRNA electroporation	[176]
GPC3	Hepatocellular carcinoma (HCC)	CD28 + CD3ζ	NK-92 and Primary human NK cells from PBMCs	Lentiviral transduction	[177]
CEA	Colorectal cancer	CD3ζ	NK-92MI cells	Retroviral transduction	[178]
EGFR, EGFRvIII	Glioblastoma multiform (GBM)	CD28 + CD3ζ	NK-92 and NKL and Primary human NK cells from PBMCs	Lentiviral transduction	[130, 148]
EGFRvIII	Glioblastoma	DAP12	YTS cells	Lentiviral transduction	[78]
NKG2D	Osteosarcoma; prostate, colon, HCC, and breast cancer (NKG2D)	DAP10 + CD3ζ	Primary NK cells from PBMC	Retroviral transduction	[179]
NKG2D	CD73⁺ solid tumors /lung cancer	DAP10 + CD3ζ	NK-92 cells	PiggyBac transposon	[137]
NKG2D	Ovarian cancer	2B4 + CD3ζ	iPSC-derived human NK cells	PiggyBac transposon	[102]
ErbB2/HER-2	Breast/ovarian cancer/squamous cell carcinoma	CD3ζ	NK-92 cells	Retroviral transduction	[158]
ErbB2/HER-2	Ovarian and breast cancer	CD28 + CD3ζ	Primary NK cells from PBMC	Retroviral transduction	[180]
ErbB2/HER-2	Breast cancer/renal cell carcinoma (RCC)	CD28 + 4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[159]
ErbB2/HER-2	Glioblastoma	CD28 + CD3ζ	NK-92 cells	Lentiviral transduction	[149]
ErbB2/HER-2	Breast cancer	CD28 + CD3ζ	NK-92 cells	mRNA electroporation	[181]
EGFR	Renal cell carcinoma (RCC)/solid tumor	CD28 + 4-1BB + CD3ζ	NK-92 cells	Lentiviral transduction	[182]
EGFR	Breast cancer brain metastases	CD28 + CD3ζ	Primary NK cells from PBMC and NK-92 cells	Lentiviral transduction	[164]

EGFR epidermal growth factor receptor, HCC hepatocellular carcinoma, PBMC peripheral blood mononuclear cell, CEA carcinoembryonic antigen, RCC renal cell carcinoma, CAIX carbonic anhydrase IX, UCB umbilical cord blood

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ISSN: 1757-6512

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