Table 1.

CAR Antigens Being Examined in Hematological Malignancies

Target	Indication	On Tumor Target	Off-Tumor	Refs
BCMA	Multiple myeloma	Near universal expression by MM cells in most patients	Plasmacytoid, DCs	[15,68,69]
	BCMA+ B cell lymphomas and leukemias
SLAMF7	Multiple myeloma	Expression in 95% of MM	Plasma cells, NK cells, NK-like T cells, CD8+ T cells	[29,70]
CD38	Multiple myeloma	Most MM 80–100%	Early B-cells, NK cells, activated T-cells, basophils, monocytes, hematopoietic progenitors, DCs, cardiac and smooth muscle cells, cornea, gut, pancreas	[71–73]
CD138	Multiple myeloma	Most MM cells in most patients 90–100%	Epithelial cells, pre-B-cells	[74]
CD56	Multiple myeloma	Strong expression in 70–90% MM	Muscle cells, neurons, NK cells, NK-like T-cells	[75–77]
CD74	Multiple myeloma	95% of plasma cells in >50% of patients	DCs, B-cells, DC, activated-T-cells, monocytes, macrophages	[35,78]
CD40	Multiple myeloma	Variable expression most MM 70–100%	Plasma cells, DCs, APCs	[36,79]
Kappa Light Chain	Multiple myeloma	Expression in 35% of the MM	Clonogenic MM precursors, mature B-cells	[80,81]
	FL, MZL, MCL
Lewis Antigen	Multiple myeloma	Expression in 52% of MM	Epithelial cells and granulocytes	[82]
NY-ESO-1/LAGE-1	Multiple myeloma	Expression in about 34% of the HLA-A2 positive MM.	Restricted expression to germ cells and malignant tissues	[83,84]
CD19	Multiple myeloma	Expressed only on 5% of MM cells	Clonogenic MM precursors, pan-B-cell marker	[80,85]
	B-NHL, CLL, B-ALL	Nearly universal expression in B-NHL
CD229	Multiple myeloma	Expressed in all plasma cell dyscrasias, especially with plasma cells showing the CD56+ aberrant phenotype.	Expressed on T and NK cells.	[86,87]
NKG2D	Multiple myeloma	NKG2D upregulated in response to DNA damage, infection with certain pathogens, and importantly, malignancies like MM.	Present on NK cells, invariant NKT cells, γδ T- cells, CD8 T-cells, and a small fraction of CD4 T-cells.	[88]
APRIL	Multiple myeloma	A proliferation-inducing ligand (APRIL) is members of the tumor necrosis factor (TNF) family. APRIL stimulates BCMA	B lymphocytes, fibroblasts.	[89,90]
GPRC5D	Multiple myeloma	A member of the G protein-coupled receptor family	Hair follicles	[91]
FcRH5	Multiple myeloma	A member of the immunoglobulin receptor superfamily and the Fc-receptor like family.	Epstein-Barr virus- transformed lymphocytes, spleen, and the terminal ileum of the small intestine	[92]
CD79b	B-NHL, B-ALL	Expressed on the surface of 2/3 of B-NHL	B lymphocytes	[93,94]
CD20	B-NHL	Expressed by 90% of B-NHL and 40% of B-ALL	Pan-B cell marker, follicular dendritic cells	[95]
CD22	B-NHL, B-ALL, CLL	Expressed by most B-NHL, B-ALL and CLL	Epithelioid histiocytes, B lymphocytes	[62,96]
ROR1	MCL, CLL, B-ALL	Highly expressed in CLL, but less than 10% expression in B-ALL	B-lymphocyte precursors	[97,98]
CD30	Hodgkin lymphoma, B-NHL, T-NHL	Highly expressed in ALCL and classical Hodgkin lymphoma; variable expression in other PTCL and B-NHL	Granulocytes, plasma cells, activated B, T ad NK cells, monocytes	[37]
CD70	B-NHL, AML, MM, T-NHL	Highly expressed in DLBCL, FL, LPL and Hodgkin lymphoma; CLL and AML	Activated B and T cells, thymic stromal cells, NK cells, dendritic cells; Aberrantly overexpressed by multiple solid tumors	[99]
CD7	NK/T cell lymphoma, T-ALL, AML	Highly expressed in T-ALL and most NK cell lymphomas; Expressed in a subset of myeloid malignancies	T lymphocytes, NK cells, thymocytes; variably expressed in monocytes, early myeloid cells, pre-B cells	[100,101]
CD4	PTCL, NOS, AITL, ALCL, CTCL	Expressed in many post-thymic T cell lymphomas	T helper cells, thymocytes, granulocytes, macrophages, DC	[102]
CD5	T-ALL, PTCL, CTCL	Uniformly expressed on T-ALL; Variable expression in PTCL and CTCL	Expressed on virtually all peripheral T lymphocytes, thymocytes;	[66,103]
TCR (TRBC1)	PTCL, NOS, AITL, ALCL	>95% of PTCL homogeneously express either TRBC1 or TRBC2	T lymphocytes	[104,105]
CD37	B-NHL, CLL, PTCL, CTCL, T-PLL	Highly expressed in both B-NHL and T-NHL	Expressed on non-neoplastic B and T cells	[102]

Abbreviations: BCMA, B-cell maturation antigen; DC, dendritic cells; B-ALL, B cell acute lymphoblastic leukemia; CLL, chronic lymphocytic leukemia; B-NHL, B cell non-Hodgkin lymphoma; NK, Natural Killer; APC, antigen presenting cell; MM, multiple myeloma; ROR1, receptor tyrosine kinase-like orphan receptor 1; PTCL; NOS, peripheral T cell lymphoma; not otherwise specified; AITL, angioimmunoblastic T cell lymphoma; ALCL, anaplastic large cell lymphoma; CTCL, cutaneous T cell lymphoma; T-PLL, T-cell prolymphocytic leukemia; T-NHL, T cell non-Hodgkin lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma.