Fusion proteins monoclonal antibodies

A note on our terminology consistent with our understanding of the industry, we use the term biopharmaceuticals - representing molecules like recombinant proteins, monoclonal antibodies, fusion proteins. 

The most promising types of biologic response modifiers are monoclonal antibodies, cytokines, and fusion proteins.1 Monoclonal antibodies may be chimeric (fused mouse and human segments designated -ximab ), humanized with intermittent murine sequences (designated -zumab ), human backbone with monkey sequences, or fully human.40... 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

Liossis, S. and Tsokos, G. 2005. Monoclonal antibodies and fusion proteins in medicine. Journal of Allergy and Clinical Immunology 116(4), 721-729. 

Alternatively, GFP can be visualized using rabbit polyclonal antibody raised against GFP purified directly from A. victoria. This anti-GFP antibody facilitates the detection of native GFP, recombinant GFP, and GFP-fusion proteins both by immunofluorescence and brightfield microscopy, as well as by western blot analysis and immunoprecipitation. Direct anti-GFP conjugates made from a complete serum or from an IgG fraction are available from Invitrogen (http //www.invitrogen.com/ site/us/en/home.html). Additional options for your research offered by Invitrogen include two mouse monoclonal antibodies and a chicken IgY fraction. 

The membrane fusion activity is probably a function of the El protein, since the hemolytic activity of Sindbis virus can be inhibited by monoclonal antibodies specific for El (Chanas et al., 1982). Moreover, studies using cDNA molecules coding for the spike proteins have shown that if the spike protein is expressed at the cell surface, fusion between cells is induced at low pH. However, when the p62 protein is expressed alone, no fusion occurs (Kondor-Koch et al., 1983). 

Monoclonal) antibodies Other characteristics of late endosomes are unique lipids or proteins associated with the different compartments. These can be used as a target for (monoclonal) antibodies. Often, also the recombinant GFP-fusion proteins are available (such as GFP-Rab5 and GFP-RhoB). 

Three TNF antagonists are currently approved for the treatment of RA etaner-cept (ETN), infliximab (INF), and adalimumab. ETN a fusion protein of two identical chains of the recombinant human TNF receptor, p75, fused with the Fc portion of human immunoglobulin (Ig) G1 binds to soluble TNF-a in vivo. INF and adalimumab are both monoclonal antibodies to TNF-a INF is chimeric, and adalimumab is fully humanized. Both bind to soluble TNF-a, preventing TNF-a from binding to its receptors on cell surfaces. INF can also bind transmembrane TNF-a, fix complement, and cause cell lysis. 

Even greater flexibility was achieved by genetic fusion of streptavidin with protein A [153,154]. Protein A specifically binds the Fc domain of IgG immunoglobulins of almost all mammals without inhibiting the antigen binding activity of the antibody. The streptavidin-protein A fusion construct was used for the assembly of complexes of biotinylated P-galactosidase and different monoclonal antibodies specific for tumour cell receptors. As a result these complexes were efficiently delivered into several cancer cell lines [154]. 

Ternant D, Paintaud G. Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins. Expert Opin Biol Ther 2005 Suppl 1 837-47. 

Palivizumab is a monoclonal antibody that binds to the fusion protein of respiratory syncytial virus, preventing infection in susceptible cells in the airways. It is used in neonates at risk for this viral infection and reduces the frequency of infection and hospitalization by about 50% (see Chapter 49). 

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