New antibody approaches to lymphoma therapy

Table 1 Anti-CD20 monoclonal antibodies currently approved or being investigated in clinical trials for B-cell lymphomas

mAb	Type of CD20 antibody*	Generation**	Structure	Mechanism of action (ADCC/CDC/PCD)	Comparison to rituximab	Indications tested	Phase of development	References
Rituximab	I	1	IgG1 Human Mouse chimeric	++/++/+	-	NHL/CL/DLBCL	FDA approved for NHL, CLL, DLBCL	[8]-[11]
Obinutuzumab (GA101; Gazyva™)	II	3	Murine bly-l derived humanized IgG1	++++/-/++++	Superior PCD/ADCC; no CDC	CLL/NHL	Phase 2/3 Approved in 2013 for untreated CLL in combination with CIb	[12]-[20]
Ofatumumab (HuMax-CD2O; Arzerra®)	I	1	Fully human IgG1	+++/++++/++	Superior CDC, decreased PCD	CLL/NHL	Phase 2/3 Approved for untreated CLL in combination with CIb & refractory CLL	[21]-[35]
Veltuzumab	I	2	Humanized IgG1	++/++/+	Longer ”off-rate”, more avid CD20 binding. can be given subcutaneously	R/R NHL/CLL	Phase 1/2	[36]-[38]
Ocrelizumab	I	2	Humanized fusion IgG1	+++/+/+	Enhanced binding to FCyRIIa	NHL	Phase 3	[39]
LY2469298	I	3	Modified Fc region human IgG1	+++/++/++	Enhanced Fc binding; superior ADCC	NHL	Phase 1/2	[40]
BM-ca	I/II***	3	Humanized IgG	++++/+++/++++	Different epitope, superior ACDD, CDC and PCD	NHL	Phase 1	[42]-[44]

ADCC: Antibody dependent cellular cytotoxicity; CDC: Complement dependent cytotoxicity; CIb: chlorambucil; CLL: Chronic lymphocytic leukemia; DLBCL: Diffuse large B cell lymphoma; PCD: programmed cell death; mAb: Monoclonal antibody; Moa: Mechanism of action; NHL: Non-Hodgkin lymphoma.
*Type of mAb: compared to a type I mAb, a type 2 mAb does not evoke a complement response, however, may have increased PCD/ADCC.
**Generations of mAB.
1^st generation: originally approved mAB against a clinically validated target 2^nd generation: follow-up antibodies with improved variable domains that target the same epitopes with higher or lower affinity, or have different antibody formats, e.g. Pegylation and Fc-fusion proteins. 3^rd generation: target different epitopes or trigger other mechanisms of action; often engineered for improved Fc-associated immune functions or half-life.
***BM-ca demonstrates properties of both Types I and II mAbs.

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