Chimaeric antibodies

Erbitux (cetuximab chimaeric antibody raised ImClone Systems Treatment of EGF receptor-... 

The first strategy entails production of chimaeric antibodies, consisting of mouse variable regions and human constant regions (Figure 13.9). The chimaeric antibody would display the specificity of the original murine antibody, but would largely be human in sequence. 

Figure 13.9 Production of chimaeric (a) and humanized (b) antibodies (via recombinant DNA technology). Chimaeric antibodies consist of murine monoclonal VH and VL domains grafted onto the Fc region of a human antibody. Humanized antibody consists of murine CDR regions grafted into a human antibody...

It was hoped that such chimaeric antibodies, when compared with murine antibodies, would be ... 

When compared with human monoclonals (half-life 14-21 days), murine monoclonals administered to humans display a relatively short half-life (30-40 h). Chimaerization increased serum half-life by fivefold, with typical values of 230 h being recorded (Table 13.4). A prolonged half-life is desirable if the antibody is to be used therapeutically, as it decreases the required frequency of product administration. Chimaeric antibodies also allow activation of Fc-mediated functions (e.g. activation of complement, etc.), as this domain displays human sequence. 

Reduced immunogenicity was expected, as only a minor proportion of chimaeric antibodies are murine in origin. Furthermore, the FIAMA response is normally directed largely at epitopes... 

It is a chimaeric antibody containing murine light and heavy chain variable sequences and human constant region sequences. It is produced by genetically transformed CHO cells. 

Cetuximab (Ebritux ) is used in the treatment of advanced colorectal cancer. It is a chimaeric antibody produced in a murine myeloma cell line. 

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