RICHARD BEGENT:  SATURDAY 01 APRIL 2006, 09:35

Engineered Antibodies and Clinical Applications

Richard Begent, Kerry Chester, Berend Tolner, A. Huhalov, R. Barbara Pedley, Astrid Mayer
Royal Free and University College Medical School, UCL, Oncology, London, UK

Recombinant DNA technology has the potential to produce more effective antibody-therapeutic targeting systems than is possible with naturally occuring antibody molecules. Examples in antibody-dirested enzyme prodrug therapy (ADEPT) and radioimmunotherapy will be discussed The design requirements are efficient tumor localization, a well defined and biologically active molecule, control of blood clearance, favorable biodistribution in normal tissues, cost effective production and low immunogenicity. An antibody-enzyme molecule containing two single chain Fv anti-CEA molecules genetically fused with carboxypeptidase has be designed and produced with these characteristics. Clinical trial shows that it fulfils the design critera which were not attainable with with chemical conjugates of antibody and enzyme. A further group of molecules in which single chain Fv anti-CEA antibodies are fused with human serum albumin have been designed for radioimmunotherapy and are being investigated with a view to clinical trial. When limitations of a molecule are found in preclinical or clinical studies, there is often potential to modify the targeting molecule by recombinant DNA technology so that an original design can be iteratively improved.

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