Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: A folate receptor beta-specific human monoclonal antibody recognizes activated macrophage of rheumatoid patients and mediates antibodydependent cell-mediated cytotoxicity. | Feng et al. Arthritis Research Therapy 2011 13 R59 http content 13 2 R59 RESEARCH ARTICLE Open Access A folate receptor beta-specific human monoclonal antibody recognizes activated macrophage of rheumatoid patients and mediates antibodydependent cell-mediated cytotoxicity Yang Feng1 Jiayin Shen2 Emily D Streaker3 Michael Lockwood4 Zhongyu Zhu1 Philip S Low2 and Dimiter S Dimitrov1 Abstract Introduction Folate receptor beta FRp is only detectable in placenta and limited to some hematopoietic cells of myeloid lineage in healthy people. Studies have indicated that FRp is over-expressed in activated macrophages in autoimmune diseases and some cancer cells. In this study we aimed to develop an FRp-specific human monoclonal antibody mAb that could be used as a therapeutic agent to treat rheumatoid arthritis and other autoimmune diseases as well as FRp positive cancers. Methods Functional recombinant FRp protein was produced in insect cells and used as antigen to isolate a mAb m909 from a human naive Fab phage display library. Binding of Fab and IgG1 m909 to FRp was measured by ELISA surface plasmon resonance immune fluorescence staining and flow cytometry. Antibody-dependent cell-mediated cytotoxicity ADCC was evaluated with FRp positive CHO cells as target cells and isolated peripheral blood monocytes as effector cells in an in vitro assay. Results Fab m909 bound with relatively high affinity equilibrium dissociation constant 57 nM to FRp. The IgG1 m909 showed much higher femtomolar avidity as measured by ELISA and it bound to FRp positive cells in a dose-dependent manner but not to parental FRp negative cells. m909 did not compete with folate for the binding to FRp on cells. m909 was not only able to select FRp positive activated macrophages from synovial fluid cells of arthritis patients as efficiently as folate but also able to mediate ADCC in FRp positive cells. Conclusions Unlike folate-drug conjugates m909 selectively binds to FRp does not .
