Table 1.

Preclinical studies of BiTE

Indication	scFv1-target	scFv2-target	scFv1 linker	scFv2 linker	scFv1-scFv2 linker	Model	Model experiment results	Ref
AML	CD33	CD3	NR	NR	NR	Immunodeficient mice	Volume decreases by about 1000 mm3	[27]
AML	CD123	CD3	NR	NR	NR	Xenograft mice model	Leukemia eradication	[28]
AML	CLEC12A	CD3	NR	NR	NR	Human xenograft mouse model	Median survival increases 14.5 days	[29]
MM	BCMA	CD3ε	NR	NR	NR	L-363 xenograft model	Median survival increases 9 days	[30]
MM	A2/NY-ESO-1157	CD3ε	NR	NR	SGSG	Tumor-bearing mice model	Tumor growth was significantly suppressed	[15]
Solid tumors	EpCAM (CD326)	CD3	NR	NR	NR	4T1 orthotopic breast cancer	Reduction of volume was 82% after treatment with 5 μg/kg	[40]
Solid tumors	mu-EpCAM (CD326)	CD3	NR	NR	NR	NOD/SCID mouse models	Tumors eliminate	[32]
Solid tumors	CEA	CD3ε	(G4S) 3	NR	NR	Xenograft mice model	Significantly inhibited tumor growth	[45]
HCC	Glypican 3 (GPC3)	CD3	(G4S) 3	(G4S) 3	G4S	Mice model	Tumor weight decreases about 1 g	[48]
HCC	TfR	CD3	(G4S) 3	(G4S) 3	ASTGS	Xenograft model	Volume decreases by about 1000 mm3	[16]
SCLC	DLL3	CD3	NR	NR	NR	Orthotopic mice model	Tumor regression	[20]
GBM	EGFRvIII	CD3	(G4S) 3	(G4S)3	G4S	Orthotopic xenograft models	Durable complete cure at rates up to 75%	[57]
Solid tumors	GD2	CD3	NR	NR	NR	Co-culture	Effectively killed GD2-positive neuroblastoma cell lines	[59]
Solid tumors	PSMA	CD3ε	NR	NR	NR	Immunodeficient NOD/SCID mice model	Complete tumor eradication	[65]
Solid tumors	CLDN6	CD3	(G4S) 3	(G4S) 3	(G4S) 3	NSG mice xenograft tumors model	Nearly complete tumor eradication	[26]
Solid tumors	EphA2	CD3	(G4S) 3	(G4S) 3	NR	SCID xenograft model	2 log or greater reduction in their tumor signal	[18]
Both hematopoietic tumors and solid tumors	CD206	CD3ε	NR	NR	GGGGS	Malignant ascites fluids	Triggering robust T cell activation and cytotoxicity	[21]
Both hematopoietic tumors and solid tumors	FRβ	CD3ε	NR	NR	GGGGS	Malignant ascites fluids	Greatly diminished	[21]
Both hematopoietic tumors and solid tumors	ESK1	CD3ε	NR	NR	NR	NSG mice model	Survival time extended by about one month	[71]
Both hematopoietic tumors and solid tumors	B7H6	CD3ε	(G4S) 3	(G4S) 3	(G4S) 3	Co-cultured	Produce IFN-γ, not pro-inflammatory monocytes	[70]
HCMV	gB	CD3	NR	NR	NR	Co-cultured	Secrete IFN-γ and TNF	[23]
AIDS	gp120	CD3ε	(G4S) 3	(G4S) 3	SG4S	Co-cultured	>90% HIV inhibition at 1 μg/ml	[24]

NR, not reported; ALL, acute lymphoblastic leukemia; MM, multiple myeloma; SCLC, small cell lung cancer; AML, acute myelocytic leukemia; HCC, hepatocellular carcinoma; GBM, glioblastoma; AIDS, acquired immunodeficiency syndrome; HCMV, human cytomegalovirus.