A folate receptor beta-specific human monoclonal antibody recognizes activated macrophage of rheumatoid patients and mediates antibody-dependent cell-mediated cytotoxicity

摘要: Folate receptor beta (FRβ) is only detectable in placenta and limited to some hematopoietic cells of myeloid lineage healthy people. Studies have indicated that FRβ over-expressed activated macrophages autoimmune diseases cancer cells. In this study we aimed develop an FRβ-specific human monoclonal antibody (mAb) could be used as a therapeutic agent treat rheumatoid arthritis other diseases, well positive cancers. Functional recombinant protein was produced insect antigen isolate mAb, m909, from naive Fab phage display library. Binding IgG1 m909 measured by ELISA, surface plasmon resonance, immune fluorescence staining, flow cytometry. Antibody-dependent cell-mediated cytotoxicity (ADCC) evaluated with CHO target isolated peripheral blood monocytes effector vitro assay. bound relatively high affinity (equilibrium dissociation constant 57 nM) FRβ. The showed much higher (femtomolar) avidity it dose-dependent manner, but not parental negative did compete folate for the binding on able select positive, synovial fluid patients efficiently folate, also mediate ADCC Unlike folate-drug conjugates, selectively binds FRβ, does recognize FRα, has at least one function. alone potential eliminate Because binding, can conjugates combination therapy. valuable research reagent.