Rituximab and Obinutuzumab for B-cell Lymphoma

Rituximab

Rituximab is the first approved anti-CD20 monoclonal antibody for the treatment of non-Hodgkin lymphoma (NHL) in the world and can be used to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL).

• Mechanisms of Rituximab
• Antibody-dependent cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).
• Direct cytotoxicity.
• Complement-dependent cytotoxicity (CDC).

Among them, ADCC/ADCP is considered to be the most important mechanism of Rituximab.

The success of Rituximab proves that the CD20 antigen is a very desirable target. Advances in technology have led to the continuous optimization of monoclonal antibodies and the gradual evolution to humanized and fully human monoclonal antibodies. Type II anti-CD20 monoclonal antibody Obinutuzumab is a new generation of humanized anti-CD20 antibody modified by glycosylation.

Obinutuzumab

Obinutuzumab is the first individualized, glycosylated type II anti-CD20 monoclonal antibody in the world, which brings new hope to MCL patients due to its higher antibody stability, stronger DCD and ADCC.

You can find more information about Obinutuzumab by clicking here!

Difference Between Rituximab and Obinutuzumab

• Rituximab is a human-mouse chimeric monoclonal antibody, and the variable region of the antibody comes from the murine source, while Obinutuzumab is a humanized monoclonal antibody, so the immunogenicity of Obinutuzumab is lower.
• Obinutuzumab has a stronger (35 times) ADCC effect than Rituximab, and DCD is also stronger than Rituximab, while CDC is weaker than Rituximab.
• As a type II antibody, Obinutuzumab does not internalize after binding to CD20. Moreover, the Fc section of Obinutuzumab is modified by glycosylation, which increases the affinity of the antibody for effector cells.

Fig.1 Mechanisms of Rituximab and Obinutuzumab

Method:

Obinutuzumab and Rituximab (1-100 μg/ml) treat PMBL cells, respectively. ADCC is performed with ex vivo amplification of natural killer cells. Mice are xenografted with luciferase-expressing Karpas 1106P cells and treated once every 7 days for 8 weeks. Monitor tumor burden by IVIS lineage.

Results:

The following is some experimental data from this article：

Fig.2 The expression of CD20 mRNA and protein.

Fig.3 Cell proliferation and apoptotic activity after obinutuzumab treatment.

Fig.4 Obinutuzumab is more effective in ADCC activity.

Conclusion:

Compared with Rituximab, Obinutuzumab reduced PMBL proliferation, significantly enhanced natural killer cytotoxicity, and prolonged the overall survival of humanized PMBL xenografted NOD scid γ mice.

References

1. Freeman, C.L.; Sehn, L.H. A tale of two antibodies: obinutuzumab versus rituximab. British Journal of Haematology. 2018, 182(1): 29-45.
2. Chu, Y.; et al. Obinutuzumab (GA101) vs. rituximab significantly enhances cell death, antibody-dependent cytotoxicity and improves overall survival against CD20+ primary mediastinal B-cell lymphoma (PMBL) in a xenograft NOD-scid IL2Rgnull (NSG) mouse model: a potential targeted agent in the treatment of PMBL. Oncotarget. 2020, 11(32): 3035–3047.