Table 1.

Preclinical and clinical investigations of CAR-modified primary human natural killer cells.

	Antigen	Signaling domain	Target cells	Efficacy	Reference or ClinicalTrials.gov identifier
Preclinical studies with cell lines as targets	CD19	4-1BB/CD3ζ	Acute lymphatic leukemia cell lines	+++	(15)
	HER-2	CD28/CD3ζ	Ovarian cancer cell line and breast cancer cell line	+	(17)
	Disialoganglioside 2 (GD2)	2B4/CD3ζ	Neuroblastoma cell line	+++	(18)
	CD19	2B4/CD3ζ	ALL cell lines	+++	(18)
	CD19	4-1BB/CD3ζ	B-ALL cell line	+++	(19)
	CD19	4-1BB/CD3ζ	B-ALL cell lines and B cell lymphoma cell lines	++ to +++	(20)
	Natural killer group 2 member D ligands	DAP10/CD3ζ	ALL cell lines and several solid tumor cell lines	+ to +++	(21)
	HER-2	CD28/CD3ζ	HER-2-expressing cell lines	n.a.	(22)
	CD19	4-1BB/CD3ζ	B-ALL cell lines	+	(23)
	CS1	CD28/CD3ζ	Myeloma cell lines	Data not shown	(24)
	CD20	4-1BB/CD3ζ	CD20+ B-cell non-Hodgkin lymphoma cell lines	++ to +++	(25)
	Epidermal growth factor receptor (EGFR)	CD28/CD3ζ	Glioblastoma cell lines	+	(26)
	Prostate stem cell antigen (PSCA)	DAP12	several PSCA+ tumor cells	(+) to +++	(27)
	CD19	CD28/4-1BB/CD3ζ	CD19+ leukemia cell line	+ to +++	(28)
	EGFR	CD28/CD3ζ	Breast cancer cell lines	+	(29)
	GD2	CD28/4-1BB/CD3ζ	Ewing sarcoma cell lines	+ to ++	(30)
Preclinical studies with patient malignant cells as targets	CD19	4-1BB/CD3ζ	Acute lymphatic leukemia	+++	(15)
	CD19	2B4/CD3ζ	Acute lymphatic leukemia	+++	(18)
	CD19	4-1BB/CD3ζ	B-CLL cells	+++	(19)
	CD19	4-1BB/CD3ζ	B-ALL cells	+	(23)
	EGFR	CD28/CD3ζ	Glioblastoma stem cells	(+)	(26)
Clinical trials	CD19	4-1BB/CD3ζ	B-lineage acute lymphoblastic leukemia	n.a.	NCT 00995137
	CD19	4-1BB/CD3ζ	B-lineage acute lymphoblastic leukemia	n.a.	NCT 01974479
	CD19	CD28/CD3ζ	B-lymphoid malignancies	n.a.	NCT 03056339

(+), cytotoxicity <25%; +, cytotoxicity 25–49%, ++, cytotoxicity 50–75%, +++, cytotoxicity >75%.