Target construction

Other limitations of mouse/rat models are that tumour growth is different in the animal model compared to the situation in man.Tumour growth is more rapid in the rat/mouse model which has an effect on vascularization and intra-tumoural pressure for example. These factors can, as discussed in Section 8.4, have great impact on tumour penetration and uptake of the MAb-based drug-targeting constructs. 

Development of Proteinaceous Drug Targeting Constructs Using Chemical and Recombinant DNA Approaches... 

Table 11.1. Proteins used in drug targeting constructs.

Many natural protein hgands bind to their receptors via interactions of a specific area of the protein backbone. The receptor binding domain of such a protein can be transferred into another protein, for instance a therapeutically active one. This technique is commonly applied in the preparation of recombinant targeting constructs, and will be discussed in Section 11.8.2. 

As mentioned in Section 11.2, a special class of proteinaceous targeting constructs are those in which a therapeutic protein is used as the active drug substance. In such a preparation, the protein is redirected to the target tissue by the attachment of site-directing ligands such as those discussed in Section 11.3. For instance, interferon beta (IFN- 3) can be redirected to the liver by enz5matic desialylation in a procedure similar to that described earlier for fetuin (Section 11.3.1). The resultant asialo-IFN- 3 was found to have an in vivo anti-viral effect when tested in a hepatitis B model in athymic nude mice [54]. 

Recombinant Domains as Building Blocks for Drug Targeting Constructs... 

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