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INTRODUCTION Soluble immune aggregates bearing intact Fc fragments are effective treatment for a variety of autoimmune disorders in mice. The better to understand the mechanisms by which Fc-bearing immune complexes suppress autoimmunity, and to develop a platform for clinical translation, we created a series of fully recombinant forms of polyvalent IgG2a(More)
CD137 (4-1BB) is a costimulatory molecule that can be manipulated for the treatment of cancer and autoimmune disease. Although it is known that agonistic antibodies (mAbs) against CD137 enhance the rejection of murine tumors in a natural killer (NK) cell- and T cell-dependent fashion, the mechanism for NK dependence is poorly understood. In this study, we(More)
P-selectin glycoprotein ligand-1 (PSGL-1) is present on leukocytes and is the major ligand for endothelial expressed P-selectin. A variety of studies strongly suggests that the N-terminal region of PSGL-1 contains the binding site for P-selectin. We hypothesized that this relatively small N-terminal peptide of PSGL-1 is sufficient to support adhesion to(More)
CD137 (4-1BB)-mediated costimulation plays an important role in directing the fate of Ag-stimulated T cells and NK cells, yet the role of CD137 in mediating B cell function is unknown. We found that CD137 is expressed in vitro on anti-Ig-stimulated peripheral blood B cells and in vivo on tonsillar B cells with an activated phenotype. In vitro CD137(More)
Altered B cell function is important in the pathogenesis of rheumatoid arthritis (RA). In this report, we show that patients with active RA have an increased frequency of CD32B low/neg cells in the CD27(+)IgD(-) memory B cell subset and that these changes are associated with phenotypic and functional B cell activation. Studies using PBMCs from healthy(More)
We developed a fully recombinant anti-CD20 protein derived from cDNA encoding one Fab domain, two IgG1 Fc regions, the IgG2 hinge, and an isoleucine zipper. This protein, called GB4542, contained both the homodimer and higher-order multimers. Binding studies revealed that GB4542 preferentially bound CD20(+) cells yet also recognized CD20(-)FcγR(+) PBMC. In(More)
Tumour antigen targeted antibodies (mAbs) can induce natural killer (NK) cells to kill tumours through antibody dependent cellular cytotoxicity (ADCC) upon engagement of NK cell expressed FcγRIIIa. FcγRIIIa polymorphisms partially dictate the potency of the ADCC response. The high affinity FcγRIIIa-158-valine (V) polymorphism is associated with more potent(More)
Agonistic monoclonal antibodies (mAbs) directed against the co-signaling molecule CD137 (4-1BB) elicit potent anti-tumor immunity in mice. This anti-tumor immunity has traditionally been thought to result from the ability of the Fab portion of anti-CD137 to function as an analog for CD137L. Although binding of CD137 by anti-CD137 mAbs has the potential to(More)
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