Rituximab

Brand Name: Rituxan

Biosimilar Brand Name: Riabni, Ruxience, Truxima

Rituximab is used to treat non-Hodgkin's lymphoma (NHL), B-cell acute leukemia (B-AL), and chronic lymphocytic leukemia (CLL), among other types of cancer.1

How Does Rituximab 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

Rituximab is bound to CD20 in a cluster.

Rituximab is an antibody drug that can recognize a specific structural motif of CD20.5,6 In addition, rituximab 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.7,8 C1q then recruits various proteins to be inserted into the surface of the cell.9

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.9 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. RITUXAN. U.S. Food and Drug Administration (2021).

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. Reff, M. E. et al. Depletion of B Cells In Vivo by a Chimeric Mouse Human Monoclonal Antibody to CD20. Blood 83, 435-445 (1994).

6. Binder, M., Otto, F., Mertelsmann, R., Veelken, H. & Trepel, M. The epitope recognized by rituximab. Blood 108, 1975-1978 (2006).

7. Rougé, L. et al. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab. Science 367, 1224-1230 (2020).

8. van Meerten, T., van Rijn, R. S., Hol, S., Hagenbeek, A. & Ebeling, S. B. Complement-Induced Cell Death by Rituximab Depends on CD20 Expression Level and Acts Complementary to Antibody-Dependent Cellular Cytotoxicity. Clinical Cancer Research 12, 4027-4035 (2006).

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