Monoclonal antibodies Humanized

Recombinant humanized monoclonal antibodies have been used recently to target antigens that are preferentially located on cancer cells. Examples include trastuzumab and rituximab which are used to treat HER2 positive breast cancer and B-cell type lymphomas, respectively. Unwanted side effects include anaphylactic reactions. 

Humanized Monoclonal Antibodies. Figure 1 Schematic representation of mouse, human, chimeric and... 

Humanized Monoclonal Antibodies. Table 1 Major monoclonal antibodies FDA approved for clinical use... 

Anticytokine antibodies Infliximab Chimeric (mouse/human) monoclonal antibody against TNEa. Effective in the treatment of severe forms of rheumatoid arthritis where it can halt disease progression, or inflammatory bowel disease (EBD). 

Anticytokine receptor antibodies Basiliximab, Da-cluzimab Both are humanized monoclonal antibodies against the IL-2 receptor that block T-cell proliferation by inhibiting IL-2 and thus decrease the T-cell mediated frequency of rejection episodes in organ transplantation. 

Humanized Monoclonal Antibodies Humoral Immunity HVA Ca2+ Channels Hybridization... 

A.M. Campbell, Monoclonal Antibody and Immunosensor Technology the Production and Application of Rodent and Human Monoclonal Antibodies, Elsevier, Amsterdam (1991). 

Bevacizumab is a humanized monoclonal antibody that binds to vascular endothelial growth factor, which prevents it from binding to its receptors, ultimately resulting in angiogenesis. 

Xiang SH, Doka N, Choudhary RK, Sodroski J, Robinson JE. Characterization of CD4-induced epitopes on the HIV type 1 gpl20 envelope glycoprotein recognized by neutralizing human monoclonal antibodies. AIDS Res Hum Retroviruses 2002 18(16) 1207—1217. 

Persson, M. A., Caothien, R. H., and Burton, D. R. (1991). Generation ofdiverse high-affinity human monoclonal antibodies by repertoire cloning. Proc. Natl. Acad. Sci. USA 88, 2432-2436. 

Reiter, M., Buchacher, A., Bltlml, G., Zach, N., Steinfellner, W., Schmatz, C., Gaida, T., Assadian, A., and Katinger, H., Production of the HIV-1 Neutralising Human Monoclonal Antibody 2F5 Stirred Tank Versus Fluidized Bed Culture, Animal Cell Technology, (R. E. Spier, J. B. Griffith, and W. Berthold, eds.), p. 333, Butterworth-Heinemann, Oxford (1994)... 

Similar results were recently obtained with a human monoclonal antibody, with KDEL sequences fused to the C-termini of both heavy chains, expressed in tobacco [33]. As observed for the invertase-HDEL fusion, about 90% of the N-linked glycans on this antibody were of the high-mannose type, with 6-9 mannose residues, while a fraction contained the immunogenic P(l,2)-xylose glyco-epitope (Fig. 15.6). However, this antibody was not a(l,3)-fucosylated, a glycan modification occurring in the trans Golgi [34]. 

Synagis, a humanized monoclonal antibody, consists of several glycoforms. This indicates that a certain degree of microheterogeneity would be acceptable by the FDA. 

A number of approaches may be adopted in an attempt to reduce or eliminate protein im-munogenicity. Protein engineering (Chapter 3), for example, has been employed to humanize monoclonal antibodies (Chapter 13). An alternative approach entails the covalent attachment of polyethylene glycol (PEG) to the protein backbone. This can potentially shield immunogenic epitopes upon the protein from the immune system. 

Mabcampath (EU) or Campath (USA) alemtuzumab a humanized monoclonal antibody directed against CD52 surface antigen of B-lymphocytes) Millennium ILEX (EU) Berlex, ILEX Oncology Millennium Pharmaceuticals (USA) Chronic lymphocytic leukaemia... 

Humira (EU USA also sold as Trudexa in EU) (adalimumab r (anti-TNF) human monoclonal antibody created using phage display technology Cambridge Antibody Technologies Abbott (USA) Abbott (EU) Rheumatoid arthritis... 

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