Antibody host selection

Trace contaminants such as host cell proteins (HCPs) and DNA are deterrnined by more specialized techniques. Host cell proteins are generally deterrnined using an immunochemical assay, in which an antibody preparation, raised against a mixture of the HCPs, is used to selectively detect the total level of HCPs in the product. DNA can be deterrnined using a labeled mixture, or probe, of complimentary DNA from the host cell. 

The selected antibody fragments have been used in many applications, varying from antibody-based biochemical assays to in vivo imaging of tumours. The relative ease with which they form multimers and fusion proteins, and the possibility of high levels of expression of these molecules in a variety of different hosts, makes them ideal protein-based diagnostic and possibly future therapeutic reagents (reviewed by Hudson and Kortt) [43] (Figure 10.4). 

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

The third major difficulty in developing cold cures arises from the fact that the HRVs are RNA viruses. When presented with any selective pressure, including chemotherapeutic or antibody challenge, RNA viruses mutate rapidly [9]. This ability to mutate is most clearly illustrated in influenza viruses (RNA viruses), where new strains continuously arise to circumvent immunity in a population. Influenza A viruses have been shown to mutate around the anti-influenza drug Amantadine, after a single passage through a susceptible human host. The mutated viruses shed from a host treated with Amantadine are now resistant to Amantadine. These mutated viruses appear to be as virulent as the parent strain of virus [10]. 

The mode of action of this drug is not completely clear. It has been shown that virus absorbed to cells in vitro in the presence of 105 was susceptible to antibody inactivation several hours after infection whereas virus in a corresponding system free of 105 was not. This suggested that perhaps the drug did not inactivate the virus itself but prevented the penetration of the virus into the host cell 321 Subsequent studies have supported this conclusion 342 The manner in which cell penetration is prevented is not known. Perhaps 105 selectively binds to or in some way inhibits an enzyme essential for cell penetration or perhaps it acts by selectively binding the virus to areas of the cell wall which are not susceptible to penetration 3421. Other studies have also demonstrated a therapeutic effect of this drug 343). 

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