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Fc-dependent expression of CD137 on human NK cells: insights into 'agonistic' effects of anti-CD137 monoclonal antibodies
- Source :
- Blood. 112:699-707
- Publication Year :
- 2008
- Publisher :
- American Society of Hematology, 2008.
-
Abstract
- CD137 (4-1BB) is a costimulatory mol-ecule 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 evaluated the ability of 2 different glycoforms of a chimerized antihuman CD137 mAb, an aglycosylated (GA) and a low fucose form (GG), to react with human NK cells. Both mAbs bound similarly to CD137 and partially blocked the interaction between CD137 and CD137 ligand. However, unlike GA mAb, immobilized GG mAb activated NK cells and enhanced CD137 expression. These effects were seemingly dependent on Fc interaction with putative Fc receptors on the NK-cell surface, as only the immobilized Fc-fragment of GG was required for CD137 expression. Furthermore, CD137 expression could be enhanced with antibodies directed against non-CD137 epitopes, and the expression levels directly correlated with patterns of Fc-glycosylation recognized to improve Fc interaction with Fcγ receptors. Our data suggest that CD137 can be enhanced on NK cells in an Fc-dependent fashion and that expression correlates with phenotypic and functional parameters of activation.
- Subjects :
- Glycosylation
medicine.drug_class
Recombinant Fusion Proteins
Immunology
Receptors, Fc
Biology
Monoclonal antibody
Biochemistry
Epitope
Tumor Necrosis Factor Receptor Superfamily, Member 9
medicine
Humans
Receptor
Cells, Cultured
Immunobiology
Regulation of gene expression
Immunoglobulin Fc Fragments
CD137
Antibodies, Monoclonal
Cell Biology
Hematology
Ligand (biochemistry)
Molecular biology
Killer Cells, Natural
Gene Expression Regulation
biology.protein
Antibody
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....9fc6152d5f04edc36ae3913da635dd4f