Obinutuzumab

Brand Name: Gazyva

Obinutuzumab is used to treat chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).1

How Does Obinutuzumab 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

Obinutuzumab bound to CD20.

Obinutuzumab is an antibody drug that can recognize and bind to a specific structural motif of CD20.5,6

Antibody receptor on natural killer cells recognize obinutuzumab and releases toxins to kills cancer cells.

(1) Natural killer (NK) cells, a type of immune cell, express antibody receptors on their surface that can recognize antibodies. When these receptors bind to antibodies like obinutuzumab, NK cells get activated. (2) Active NK cells release toxins that (3) punctures and kills nearby cells.7 Since obinutuzumab specifically recognizes CD20, cells expressing the highest amounts of CD20, i.e. the lymphoma cells, are targeted for killing by natural killer cells, while most other cells are spared.5

References

1. GAZYVA. U.S. Food and Drug Administration (2022).

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. Mössner, E. et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115, 4393-4402 (2010).

6. Niederfellner, G. et al. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood 118, 358-367 (2011).

7. Wang, W., Erbe, A. K., Hank, J. A., Morris, Z. S. & Sondel, P. M. NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. Frontiers in Immunology 6, 368 (2015).