Ofatumumab

Brand Name: Arzerra

Ofatumumab is used to treat chronic lymphocytic leukemia (CLL).1

How Does Ofatumumab Work?

CD20 dimer on the surface of the cell.

CD20 is a dimeric protein found on the surface of B cell, a type of immune cell.2 The precise biological role of CD20 is not fully understood, but it may be required for optimal immune function.3

Non-B cell surface with a single CD20, followed by B cell and lymphoma cell surface with numerous CD20.

In general, non-B cells express little to no CD20 on their surface.2 On the other hand, B cells and some types of lymphoma express large amounts of CD20 on their surface, which provides a target to specifically recognize and kill these cancer cells.4

Ofatumumab is bound to CD20 in a cluster.

Ofatumumab is an antibody drug that can recognize a specific structural motif of CD20.5,6 In addition, ofatumumab can assemble multiple CD20 dimers to form a tight cluster on the surface of the cell.7

C1q binds on the top of the antibody cluster and streams of proteins are shown inserting themselves into the cell surface.

This cluster of antibodies can recruit the C1q protein to activate a part of our immune system called the complement system.5,7 C1q then recruits various proteins to be inserted into the surface of the cell.8

A pore-like membrane attack complex on the surface of the cell. Various molecules are freely passing through the complex.

The complement system culminates in the formation of the membrane attack complex, which essentially punctures a hole on the cell surface and kills the cell.8 Since rituximab specifically recognizes CD20, cells expressing the highest amounts of CD20, i.e. the lymphoma cells, are most effectively killed, while most other cells are spared.5

References

1. ARZERRA. U.S. Food and Drug Administration (2009).

2. Stashenko, P., Nadler, L. M., Hardy, R. & Schlossman, S. F. Characterization of a human B lymphocyte-specific antigen. The Journal of Immunology 125, 1678-1685 (1980).

3. Pavlasova, G. & Mraz, M. The regulation and function of CD20: an “enigma” of B-cell biology and targeted therapy. Haematologica 105, 1494-1506 (2020).

4. Press, O. W. et al. Monoclonal Antibody 1F5 (Anti-CD20) Serotherapy of Human B Cell Lymphomas. Blood 69, 584-591 (1987).

5. Teeling, J. L. et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 104, 1793-1800 (2004).

6. Teeling, J. L. et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20. The Journal of Immunology 177, 362-371 (2006).

7. Kumar, A., Planchais, C., Fronzes, R., Mouquet, H. & Reyes, N. Binding mechanisms of therapeutic antibodies to human CD20. Science 369, 793-799 (2020).

8. Walport, M. J. Complement. The New England Journal of Medicine 344, 1058-1066 (2001).