TABLE 2.

Overview of bispecific approaches that block CD47‐signal regulatory protein alpha (SIRPα) signalling

Name	Target	CD47/SIRPα blocking arm	Format	Cotreatment	Type of cancer	Progress
NI‐1701	CD19	CD47	κλ‐bispecific format 42	Rituximab	Lymphoma	Preclinical
TG‐1801	CD19	CD47	κλ‐bispecific format 43	Umbralisib, ublituximab	Lymphoma	Clinical
	CD20	CD47	scFv fusion protein 46	Obinutuzumab, daratumumab, alemtuzumab	Lymphoma	Preclinical
	CD20	CD47	CD47 nanobody fused to C‐terminal of rituximab 48		Lymphoma	Preclinical
CPO107/JMT601	CD20	rhSIRPα	IgG 1 Fc domain		CD20+ lymphoma	Clinical
HMBD004	CD33	CD47	1 + 1 IgG format 49		Acute myeloid leukaemia	Preclinical
	CD33	rhSIRPα	N‐terminal SIRPα fused to the variable light chain CD33‐targeting IgG1 52		Acute myeloid leukaemia	Preclinical
	CD123	rhSIRPα	The extracellular domain SIRPα was fused to CD123 antibody 54		Acute myeloid leukaemia	preclinical
NI‐1801	MSLN	CD47	CD47xMSLN with functional IgG1 Fc 55		Hepatocellular carcinoma	Preclinical
	MSLN	CD47	High‐affinity MSLN Ab 57		Hepatocellular carcinoma, ovarian carcinoma, gastric carcinoma	Preclinical
	CD70	rhSIRPα	Variable domain CD70 Ab with variable domain SIRPα 33		Renal cell carcinoma, Burkitt lymphoma	Preclinical
	EGFR	rhSIRPα	Knobs‐into‐holes: EGFR mAb was fused to a SIRPα variant with high affinity to CD47 61		Squamous cell carcinoma	Preclinical
IMM2902	HER2	rhSIRPα	Trap antibody receptor fusion protein		Advanced solid cancer	Clinical
PF‐07257876	PD‐L1	CD47	Unknown		Non‐small cell lung cancer, squamous cell carcinoma of the head and neck, ovarian c	Clinical
IMM0306 47	CD20	CD47	DVD‐Ig 47	Rituximab	Non‐Hodgkin lymphoma	Clinical
IBI‐322	PD‐1	CD47	IgG4 Fc domain 104	Azacitidine/decitabine (with myeloid malignancies)	Advanced solid cancer, haematological cancer, myeloid tumours	Clinical
HX009	PD‐L1	CD47	IgG4‐Fc region of anti‐PD‐1 mAb and the extracellular domain of SIRPα 105		Advanced solid cancer	Clinical
DSP‐107	4‐1BB	CD47	Fusion of the extracellular domain of SIRPα genetically fused to the extracellular domain of 4‐1BBL 110	Atezolizumab	Advanced solid cancer, non‐small cell lung cancer	Clinical
SL‐172154	CD40	rhSIRPα	Fusion protein consist of human SIRPα and CD40 L linked via a human Fc 108		Gynaecological tumours, skin, head and neck cancer	Clinical

Note: These bispecific approaches are either in the preclinical or clinical phase of development. Interestingly, they are designed in various formats and target a variety of tumour antigens.

Abbreviations: DVD‐Ig, dual‐variable domain immunoglobulin; EGFR, endothelial growth factor receptor; HER2, human epithelial growth factor receptor 2; Ig, immunoglobulin; mAb, monoclonal antibody; MSLN, mesothelin; PD‐(L)1, programmed death receptor (ligand) 1; (rh)SIRPα, (recombinant human)SIRPα; ScFv, single‐chain variable fragment.