Antibodies constant region

Biologicals. Figure 3 Fusion protein construction combination of the molecular component of interest with the constant region (Fc) of an antibody molecule, usually immunoglobulin (lg)G1 Fc, imparts the Fc function on to the molecularcomponentfortherapeutic use. The example given is ofCTLA4-lg, derivatives of which have shown clinical efficacy in the treatment of rheumatoid arthritis and transplant rejection. 

Enbrel is a product now approved for medical use that is based upon this strategy. The product is an engineered hybrid protein consisting of the extracellular domain of the TNF p75 receptor fused directly to the Fc (constant) region of human IgG (see Box 13.2 for a discussion of antibody structure) The product is expressed in a CHO cell line from which it is excreted as a dimeric soluble protein of approximately 150 kDa. After purification and excipient addition (mannitol, sucrose and trometamol), the product is freeze-dried. It is indicated for the treatment of rheumatoid arthritis and is usually administered as a twice-weekly s.c. injection of 25 mg product reconstituted in WFI. Enbrel functions as a competitive inhibitor of TNF, a major pro-inflammatory cytokine. Binding of TNF to Enbrel prevents it from binding to its true cell surface receptors. The antibody Fc component of the hybrid protein confers an extended serum half-life on the product, increasing it by fivefold relative to the soluble TNF receptor portion alone. 

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 1.10. Generalised structure of the variable and constant domains within antibodies. The variable regions (dark shading) of either the light or heavy chains are indicated as VL or VH, respectively. The light chains also possess one constant region (CL), whereas the heavy chains possess either three or four constant regions (Ch)-Ch4). depending upon the class of immunoglobulin (see text for details).

Figure 17.12 Structure of an antibody. V-region is the variable region and C-region is the constant region. Fc is the portion of the antibody that contains the effector domains. S-S is the suLphydryl Link between the chains. NH3 represents the amino terminus of each chain.

For the antibody that acts as a receptor of the B-cell, the constant region links the antigenic sites to the membrane... 

Ehrlich, G.K. and Bailon, R, Identification of peptides that bind to the constant region of a humanized IgGi monoclonal antibody using phage display, J. Mol. Recogn., 11, 121-125, 1998. 

C. Antibodies are divided into five classes based on their constant regions and immune function. 

Fig. 11. Schematic representation of the binding properties of anti-idiotype antibodies and antimetatype antibodies. V, hapten a-Id, a-type anti-idiotype antibody /i-Id, /i-type anti-idiotype antibody Met, anti-metatype antibody anti-C-region, antibodies recognizing the constant region of a primary antibody (recognizing isotype or allotype).

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