Monoclonal Antibody Based Targeting Strategies in the Clinic

Not only can antibodies by themselves function as targeted effector molecules, they can also be used as carriers for the selective delivery of drugs, toxins, enzymes, radioisotopes, and ade-noviral vectors. Most of the strategies have been applied in humans [6,75-77]. Besides these approaches, cellular cytotoxicity can be redirected towards the tumour cells using bispecific antibodies that consist of a recognition site for specific cells of the immune system and tumour-associated antigens [78,79]. This strategy circumvents the MHC restriction of antigen recognition and cellular cytotoxicity. It may therefore be exploited for the therapy of tumours which downregulate the expression of their MHC molecules and thereby avoid the normal immune response.

In the development of these antibody-based targeting strategies, modifications that have been applied to improve the efficacy of the therapy include the use of chimerized or humanized antibodies, more potent drugs and better linkages between drugs and carrier molecules. Furthermore, liposome encapsulation of drugs enabled a larger quantity of the drug to be delivered per antibody molecule [75]. The development of transgenic mice capable of making fully human antibodies now offers new opportunities for generating antibodies of therapeutic quality, and as a result has led to the revival of interest in antibody-based therapies [80].

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