Antibody engineering

Roffler, S.R., and Tseng, T.-L. (1994) Enhanced serum half-life and tumor localization of PEG-modified antibody-enzyme conjugates for targeted prodrug activation. Antibody Engineering Conference. San Diego, California. 

Presta L. Antibody engineering for therapeutics. Curr Opin Struct Biol 2003 13 519-25. 

Researchers are also testing minibodies—small pieces of antibodies engineered to be produced in bacteria or animal cells. Because of their small size, minibodies may be able do things to cells that larger, bulky antibodies cannot do. Such a minibody has recently been produced and tested in animals, and in the future may help patients with certain kinds of bleeding disorders. 

Kontermann, R. (2001). Antibody Engineering. Springer-Verlag, Berlin. 

A better understanding of antibody disposition and technical developments in antibody engineering have provided essential knowledge for transforming mouse mono-... 

Gillies, S D (1992) Design of expression vectors and mammalian cell systems suitable for engineered antibodies, in Antibody Engineering A Practical Guide (Borrebaeck, C. A K., ed.), Freeman, New York. 

Allen, D., Simon, T., Sablitzky, F., Rajewsky, K., Cumano, A. (1988). Antibody engineering for the analysis of affinity maturation of an anti-hapten response. EMBO J. 7, 1995-2001. 

McCafferty, J., Hoogenboom, H. R., and Chiswell, D. J. (1996) Antibody Engineering A Practical Approach. Oxford University Press, Oxford, UK. 

Kontermann, R. E. and Dubel, S. (eds.) (2001) Antibody Engineering. Springer Lab Manuals, Berlin, Germany. 

Harvey, B. R., Rogers, G. K., Iverson, B. I., and Georgiou, G. (2002) Anchored periplasmic expression (APEx) a new platform for library screening and affinity maturation. Conference book IBC s 13th international conference, Antibody Engineering. 

Pliickthun, A. (1991) Antibody engineering advances from the use of Escherichia coli expression systems. Bio/Technology 9,545-551. 

Ward, E. S. (1993) Antibody engineering using Escherichia coli as host. Adv. Pharmacol. 24, 1-20. 

L G. Pnesta. Antibody engineering. Curn Opin. Struct. BioL 2 593-596 (1992). 

The first therapeutic antibody approved (Orthoclone OKT-3 or Muromonab CD3, 1986) was indicated not for cancer treatment, but for controlling acute rejection of transplanted organs (kidney, heart, and liver). Nowadays, other clinical indications such as asthma, rheumatoid arthritis, psoriasis, and Crohn s disease are treated with mAbs (see Chapter 17) (Antibody Engineering and Manufacture, 2005 Monoclonal Antibodies and Therapies, 2004 Hot Drugs, 2004 Walsh, 2004). 

Antibody Engineering and Manufacture (2005), Special issue Nat. Biotechnol., vol. 23. 

Glaser SM, Yelton DE, Huse WD, Antibody engineering by codon-based mutagenesis in a filamentous phage vector system, J. Immunol., 149 3903-3913, 1992. 

Maynard J, Georgiou G. Antibody Engineering. Annu Rev Biomed Eng 2000 2 339-76. 

Antibodies that demonstrate catalytic activity. The early development of these antibodies was based on the use of haptens, which mirrored transition state intermediates for enzyme-catalyzed reactions. Catalytic antibodies can be referred to as abzymes. See Kraut, J., How do enzymes work Science 242, 533-540, 1988 Lemer, R.A. and Tramontano, A., Catalytic antibodies, Sci. Am. 258, 65-70, 1988 Green, B.S., Catalytic antibodies and biomimetics, Curr. Opin. Biotechnol. 2, 395 400,1991 Jacobs, J.W., New perspectives on catalytic antibodies. Biotechnology 9, 258-262, 1991 Blackburn, G.M., Kingsbury, G., Jayaweera, S., and Burton, D.R., Expanded transition state analogues, Ciba Found. Symp. 159, 211-222, 1991 O Kennedy, R. and Roben, R, Antibody engineering an overview. Essays Biochem. 26, 59-75, 1991 Stewart, J.D., Krebs, J.F., Siuzdak, G. et al.. Dissection of an antibody-catalyzed reaction, Proc. Natl. Acad. Sci. USA 91,7404-7409,1994 Posner, B., Smiley, J., Lee, 1., andBenkovic,... 

Paul, S. (Ed.) (1995) Antibody Engineering Protocols, Methods in Molecular Biology Vol. 51. 

The first murine monoclonal antibody was approved for marketing in 1986/ when Orthoclone (CD3-specific antibody)/ or OKT3/ was approved. NoW/ humanized antibodies/ engineered so that HAMA response is mitigated have become mainstream therapy/ with such recent successes as Raptiva/ ErbituX/ and Avastin (Table 32.1). A successful antibody also needs to be potent and specific (6). The following sections describe how engineered antibodies can be produced to meet these requirements. 

Following recent advances in antibody engineering, it is now possible to s)mthesize humanized antibodies [35]. Because of clinical applicability, antibody-based medicines are one of the biopharmaceutical categories that have attracted close attention in recent years [36]. IgG has been most frequently used for the prevention and treatment of various diseases. The CH2 region of IgG has A-linked carbohydrates (usually complex type double stranded chains) in diverse manners (O Scheme 14). It has recently been revealed that differences in the carbohydrate structure affect the effecter activity of antibodies such as antibody-dependent cellular cytotoxicity (ADCC) and their half-life in blood, inviting close attention from the viewpoint of improving the responses to antibody-based medicines [37,38,39]. 

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