CD32B, the human inhibitory Fc-gamma receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma.
Human CD32B (FcgammaRIIB), 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 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 mAb treatment of B-cell lymphoproliferative disorders.
Rankin
Christopher T
CT
MacroGenics, Rockville, MD 20850, USA.
Veri
Maria-Concetta
MC
Gorlatov
Sergey
S
Tuaillon
Nadine
N
Burke
Steve
S
Huang
Ling
L
Inzunza
H David
HD
Li
Hua
H
Thomas
Shannon
S
Johnson
Syd
S
Stavenhagen
Jeffrey
J
Koenig
Scott
S
Bonvini
Ezio
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000737:chemistry*; D001402:B-Lymphocytes / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG