Table 3.

Anti-CD47 antibody constructs developed for use in hematologic malignancy with their mechanism of action

antibody construct	antibody name	animal model	cell lines	publication	murine or human ab	mechanism of action	hematological malignancies
monoclonal antibody	B6H12	none	B lymphocytes isolated from CLL patients	Barbier et al 2009	human	apoptosis	CLL
monoclonal antibody	B6H12	none	B lymphocytes isolated from CLL patients, Jurkat cells	Bras et al 2007	human	apoptosis	CLL
monoclonal antibody	B6H12	OT-I transgenic mice, OT-II transgenic mice, OT-II/Foxp3-GFP+ double-transgenic mice	human colon cancer cell DLD1	Tseng et al 2013	human	phagocytosis	Hodgkin Lymphoma/colorectal adenocarcinoma
monoclonal antibody	B6H12.2	NSG or SCID mice transplanted with Raji cells	Burkitts lymphoma cell line Raji, DLBCL cell line SUDHL4, and NHL-17	Chao et al 2010 Cell	human	phagocytosis	B cell NHL, localized and disseminated lymphoma
monoclonal antibody	B6H12.2	sublethally irradiated NOD mice injected intravenously with AML LSCs	Raji cells, AML LSCs, MOLM13 cells (CD47 deficient)	Chao et al 2010 Sci Trans	human	phagocytosis	NHL
monoclonal antibody	B6H12.2	NSG mice engrafted with primary human ALL cells or CCRF-CEM cells	human ALL cells, CCRF-CEM human T-ALL cell line	Chao et al 2011 Cancer Res	human	phagocytosis	ALL
monoclonal antibody	B6H12.2	localized lymphoma model: NSG mice injected subQ with Raji cells	DLBCL cells (primary cells), Raji cells-NHL cell line	Chao et al 2011 Blood	human	phagocytosis	Burkitt lymphoma and DLBCL
monoclonal antibody	B6H12.2	NRJ mice injected peritoneally with primary PEL cells	PEL cells isolated from patient	Goto et al 2014	human	phagocytosis	primary effusion lymphoma (NHL)
monoclonal antibody	B6H12.2	xenografts and human bone-bearing RAG2-/gamma c-mice	RPMI 8226 human myeloma cell line NCI H929 human myeloma cell line	Kim et al 2012	murine	phagocytosis	multiple myeloma
monoclonal antibody	B6H12.2	NOG mice	human AML cells	Majeti et al 2009	human	phagocytosis	AML
monoclonal antibody	BRIC126	none	Raji- Burkitts lymphoma cell line, SUDHL4- DLBCL cell line, NHL-17-DLBCL cell line	Chao et al 2010 Cell	human	phagocytosis	NHL
monoclonal antibody	BRIC126	NSG mice engrafted with primary human ALL cells or CCRF-CEM cells	human ALL cells, CCRF-CEM human T-ALL cell line	Chao et al 2011 Cancer Res	human	phagocytosis	ALL
monoclonal antibody	BRIC126 (blocking)	NOG mice	human AML cells	Majeti et al 2009	murine	phagocytosis	AML
monoclonal antibody	SIRPα antibody	NSG mice engrafted with primary human ALL cells or CCRF-CEM cells	human ALL cells, CCRF-CEM human T-ALL cell line	Chao et al 2011 Cancer Res	murine	phagocytosis	ALL
monoclonal antibody	SIRPα antibody	NOG, Rag2 −/−, and gamma c −/− mice transplanted with HL-60, Kasumi-I, MOLM-13, and Tet-CD47 MOLM-13 cells	AML cell line MOLM-13, HL-60, Jurkat, U937, K562, and Kasumi-1 cells	Jaiswal et al 2009	murine	phagocytosis	AML
monoclonal antibody	5F9	xenograft mice injected via tail vein with human primary AML cells, nonhuman primates treated with ab for toxicokinetic profiling	Primary AML cells, SU048, SU028, SU266	Liu et al 2015 Plos One	murine	phagocytosis	AML
monoclonal antibody	5F9-G4	xenograft mice injected with human primary AML cells, nonhuman primates treated with ab for toxicokinetic profiling	Primary AML cells, SU048, SU028, SU266	Liu et al 2015 Plos One	human	phagocytosis	AML/also works on NHL when synergized with rituximab
monoclonal antibody	MIAP301 (ebioscience/biolegend) *blocks mouse SIRPα binding)	syngeneic wild type mice that were subQ inoculaed with A20 B-CLL cells	murine colon adenocarcinoma cell line MC38; murine B cell lymphoma cell line A20	Liu et al 2015 Nat Med	murine	T cell-mediated elimination of immunogenic tumors	B-CLL, colon adenocarcinoma
monoclonal antibody	2D3	NOG mice	human AML cells	Majeti et al 2009	murine	phagocytosis	AML
monoclonal antibody	2D3 (nonblocking) binds CD47 but does not block its interaction with SIRPα	OT-I transgenic mice, OT-II transgenic mice, OT-II/Foxp3-GFP+ double-transgenic mice	human colon cancer cell DLD1	Tseng et al 2013	human	phagocytosis	Hodgkin Lymphoma/colorectal adenocarcinoma
monoclonal antibody	MABL	SCID mice with JOK-1 cells	lymphocytic leukemia cell lines MOLT-4; JOK-1. human CLL cells	Sagawa et al 2011	human	apoptosis	B-CLL
monoclonal antibody	F(ab’)2 of mAb-MABL	Male SCID mice intravenously injected with CCRF-CEM or JOK-1 cells; and mice intraperitoneally with JOK-1 cells	acute lymphoblastic leukemia (CCRF-CEM) and B cell chronic lymphocytic leukemia (JOK-1)	Uno et al 2007	mice	apoptosis	ALL, B-CLL
monoclonal antibody	anti-CD47	THP-1 LSC-engrafted mice	human acute monocytic leukemia cell line THP-1	Wang et al 2015	human	phagocytosis	leukemias (targeting LSCs)
monoclonal antibody	B6H12/BRIC126	none	B-CLL human cells	Mateo et al 1999	Not specified	apoptosis	B-CLL
bivalent scFv	MABLscFv-15	SCID mice xenografted with KPMM2 cells	KPMM2 human myeloma cell line	Kikuchi et al 2004	murine	apoptosis	Multiple myeloma
scFv dimer (diabody)	MABLscFv-5	SCID mice xenografted with KPMM2 cells	KPMM2 human myeloma cell line	Kikuchi et al 2005	murine	apoptosis	multiple myeloma
sc(Fv)2 monomer (covalently linked)	MABLsc(Fv)2	SCID mice xenografted with KPMM2 cells	KPMM2 human multiple myeloma cell line	Kikuchi et al 2005	murine	apoptosis	multiple myeloma
bispecific that cotargets CD47 and CD20 (created using Rituximab and B6H12.2)	CD20-CD47 LL (long linker sequence); CD20-CD47 SL (short linker sequence)	NSG mice xenoplanted with luciferase expressing Raji cells, disseminated lymphoma mouse model	YB2/0, Raji, Daudi, Ramos, ST486 and J774 cell lines. B-CLL human cells	Piccione et al 2015	human	phagocytosis	NHL
fusion protein from IgV domain of human SIRPα fused to human IgG-moiety	hSIRPα-FC	NS-mice; NS-Idd13 mice that express a SIRPα variant that does not bind CD47	human AML cells	Theocarides et al 2012	human	phagocytosis	AML
high affinity SIRPα monomer	CV1 (in combination with rituximab or alemtuzumab	Raji cell lymphoma engrafted mice	Her2/neu+ SK-BR-3 breast cancer cells	Weiskopf et al 2013	human	phagocytosis	lymphoma
high affinity SIRPα monomer	CV1	NSG mice engrafted with CLBL-1 cells	CLBL-1 canine diffuse large B-cell lymphoma	Weiskopf et al 2016	human	phagocytosis	canine lymphoma
high affinity SIRPα variant	CV1-hIgG4	NSG mice engrafted with CLBL-1 cells	CLBL-1 canine diffuse large B-cell lymphoma	Weiskopf et al 2016	mouse	phagocytosis	canine lymphoma
high affinity SIRPα variant	Hu5F9-G4	NSG mice engrafted with CLBL-1 cells	CLBL-1 canine diffuse large B-cell lymphoma	Weiskopf et al 2016	mouse	phagocytosis	canine lymphoma