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B-cell antigens:
Key targets in the fight against hematologic malignancies
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).
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, including2-4:
- 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. PMID: 16929325
- 2.
- Riley JK, Sliwkowski MX. CD20: a gene in search of a function. Semin Oncol. 2000;27(6 suppl 12):17-24. PMID: 11225995
- 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. PMID: 10845926
- 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. PMID: 15944291