New antibody approaches to lymphoma therapy

Table 2 Monoclonal antibodies directed against non-CD20 surface epitopes

mAB	Target	Structure	Unique properties	Indication tested	Phase of development	References
Epratuzumab	CD22	Humanized IgG1	Enhanced ADCC, no PCD	NHL/DLBCL	Phase 1/2	[50]-[56]
Medi 551	CDI9	Afucosylated humanized IgG1	Enhanced ADCC, no CDC	NHL/DLBCL/ALL	Phase 1/2	[60],[61]
Lucatumumab	CD4O	Humanized IgG1	Also being tested in myeloma. ADCC	NHL/CLL/HL/MZL/MALT	Phase 1/2	[64],[69],[70]
Dacetuzumab	CD4O	Humanized IgG1	Partial agonist. Enhanced ADCC/CDC/PCD	DLBCL	Phase 1	[71]-[76]
Alemtuzumab (Campath®)	CD 52	Humanized IgG1	Enhanced ADCC/CDC/PCD	CLL/T-Cell NHL Approved for del17p CLL	Phase 2/3	[81]-[89]
Mogalizumab	CCR4	Afucosylated humanized IgG1	Enhanced ADCC	PTCL/CTCL	Phase 1/2	[91]-[98]
Pidilizumab (CT-011)	PD-1*	Humanized lgG1 Kappa recombinant	Reverses T-cell anergy	NHL/DLBCL	Phase 1/2	[101]-[113]
Blinatumomab	BiTE (CD3/CD19)	Single-chain bispecific antibody construct with variable regions of two antibodies.	Bispecific T-cell Engager	DLBCL/ALL	Phase 2/3	[118]-[120]

ADCC: Antibody dependent cellular cytotoxicity; ALL: Acute lymphoblastic leukemia; BiTE: Bispecific T-cell Engager; CDC: Complement dependent cytotoxicity; CLL: Chronic lymphocytic leukemia; CTCL: Cutaneous T Cell Lymphoma; DLBCL: Diffuse large B cell lymphoma; HL: Hodgkin lymphoma; mAB: Monoclonal antibody; MALT: Mucosa associated Lymphoid tissue lymphoma; Moa: Mechanism of action; MZL: Marginal zone lymphoma; NHL: Non Hodgkin lymphoma; PCD: programmed cell death; PTCL: Peripheral T Cell Lymphoma.
*PD1 is mainly expressed on regulatory T cell surface, while its ligand PDL-1 is often expressed on malignant cells. Stimulation of this pathway results in immune anergy towards malignant cells.

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