Targeting CD20:
B-cell antigens as targets in hematologic malignancies

CD20

B-cell biology and its role in cancer is an area of intense research at Genentech, a member of the Roche Group. B cells are a fundamental component of the body's immune system. However, like most cells in the body, B cells can become cancerous—leading to diseases such as non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL).

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Targeting B-cell surface antigens that are highly expressed in B-cell malignancies with monoclonal antibodies may lead to¹

• Apoptosis or direct cell death of cancer cells
• Identification and destruction of the cancer cells by immune-effector cells in a process called antibody-dependent cell–mediated cytotoxicity (ADCC)
• Facilitation of the binding of the complement system—proteins that destroy the cell membrane integrity—in a process called complement dependent cytotoxicity (CDC)

B-cell–specific proteins, such as CD20, are highly expressed on normal and malignant B cells.²

CD20 expression is specific to B cells during most stages of B-cell development³

• CD20 is typically not internalized, downregulated, or shed³
• CD20 is highly expressed on malignancies of B-cell precursors and mature B cells, including^2-4:
  • Follicular NHL, diffuse large B-cell lymphoma (DLBCL), and CLL

References:

1.

Imai K, Takaoka A. Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer. 2006;6:714-727.

2.

Riley JK, Sliwkowski MX. CD20: a gene in search of a function. Semin Oncol. 2000;27(6 suppl 12):17-24.

3.

Golay J, Zaffaroni L, Vaccari T, et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000;95:3900-3908.

4.

Wojciechowski W, Li H, Marshall S, et al. Enhanced expression of CD20 in human tumor B cells is controlled through ERK-dependent mechanisms. J Immunol. 2005;174:7859-7868.