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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2384-2391.
Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-05-020602.


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Submitted January 12, 2006
Accepted May 23, 2006

CD32B, the human inhibitory Fc-{gamma} receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma

Christopher T Rankin, Maria-Concetta Veri, Sergey Gorlatov, Nadine Tuaillon, Steve Burke, Ling Huang, David Inzunza, Hua Li, Shannon Thomas, Syd Johnson, Jeffrey Stavenhagen, Scott Koenig, and Ezio Bonvini*

MacroGenics Inc., Rockville, MD, USA

* Corresponding author; email: bonvinie{at}macrogenics.com.

Human CD32B (Fc{gamma}RIIB), the low affinity inhibitory receptor for IgG, is the predominant Fc- receptor (FcR) present on B-cells. Immunohistochemical and expression studies have identified CD32B expression in a variety of B-cell malignancies, suggesting that CD32B is a potential immunotherapeutic target for B-cell malignancies. A high-affinity monoclonal antibody (mAb 2B6), from a novel panel of anti-human CD32B-specific mAbs was chimerized (ch2B6) and humanized (hu2B6-3.5). Both ch2B6 and hu2B6-3.5 were capable of directing cytotoxicity by peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages against B- lymphoma lines in vitro. In a human B-cell lymphoma mouse xenograft model, administration of ch2B6 or hu2B6- 3.5 reduced tumor growth rate and improved tumor-free survival. Both the in vitro and in vivo activities of 2B6 required an intact Fc, suggesting an FcR-mediated mechanism of action. These data support the hypothesis that CD32B is a viable target for monoclonal antibody treatment of B-cell lymphoproliferative disorders.


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