【摘 要】
:
Monoclonal antibodies produced in mammalian host cells contain an N-linked glycosylation site at Asn 297 of each heavy (two per intact antibody molecule).Glycans on antibodies are typically complex bi
【机 构】
:
Early Stage Cell Culture BioProcess Research & Development Genentech Inc.USA
【出 处】
:
中国上海第七届国际新药发明科技年会
论文部分内容阅读
Monoclonal antibodies produced in mammalian host cells contain an N-linked glycosylation site at Asn 297 of each heavy (two per intact antibody molecule).Glycans on antibodies are typically complex biatennary structures with very low or no bisecting N-acetylglucosamine and high levels of core fucosylation.Non-fucosylated structures have been shown to be associated with dramatically increased in vitro antibody-dependent cellular cytotoxicity (ADCC) activity leading improved therapeutic protein efficacy possibly.Using small inhibitory RNA (siRNA) technology,we have been able to significantly knock down alpha-l,6-fucosyltransferase (FUT8) resulting in therapeutic antibodies with low fucose content and enhanced Fc receptor binding and enhanced ADCC activity.Using Zinc finger nucleases targeted against FUT8 gene,we developed in-house FUT knockout (FUT8KO) host cells.Antibodies generated from this FUT8KO host are afucosylated.
其他文献
HIV-1 infection begins with the binding of envelope glycoprotein surface subunit 120 to CD4 and a co-receptor CXCR4 or CCR5,triggering a series of conformational changes in the Env transmembrane subun
Several series of indole and azaindole derivatives,derived from the screening lead 1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (BMS-216),were characterized as inhibitors of HIV-1.The
The monoclonal antibody (mAb) D32.10 generated by HCV particles recognizes a discontinuous epitope encompassing three regions E1 (aa297-306),E2A(aa480-494) and E2B(aa613-621) juxtaposed on the surface
The high prevalence of hepatitis C virus (HCV) infection and limited treatment options provide an opportunity to develop new therapeutics.The HCV NS3/4A serine protease is an essential enzyme for the
Kinome,which refers to the entire kinase groups in an organism,is composed of over 500 different kinases.Extracellular stimuli transmit signals into a cell by activating their target kinases.Several k
The insulin-like growth factor/IGF/signaling system plays an important role in the regulation of cell proliferation in many tissues.The IGF system is comprised ofIGF ligands,cell surface receptors/IGF
Pancreatic cancer is one of the most lethal forms of human cancer.The current first-line treatment is based on Gemcitabine,a nucleoside drug,which is only moderately effective,yielding merely a 12% re
1.The multidrug resistance phenomenon (MDR) impairs drug efficiency,leading to chemotherapeutic failure and hence causing a strong impact on disease outcome and patient survival.MDR can be mediated by
Targeting tubulin in rapidly dividing tumor cells is a sound strategy for cancer therapy.Despite recent advances in this field,identification of both potent and selective antimitotic molecules affecti
Dihydroartemisinin (DHA),a semisynthetic derivative of artemisinin,has exhibited the strongest antimalarial activity among the derivatives of artemisinin.There is growing evidence that DHA has some im