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

From: New antibody approaches to lymphoma therapy

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]
  1. 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.
  2. *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.
  3. **Generations of mAB.
  4. 1st generation: originally approved mAB against a clinically validated target 2nd 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. 3rd generation: target different epitopes or trigger other mechanisms of action; often engineered for improved Fc-associated immune functions or half-life.
  5. ***BM-ca demonstrates properties of both Types I and II mAbs.