Recombinant monoclonal antibodies in tumor therapy

The application of monoclonal antibodies (MAb) of non human origin in the treatment of human diseases is hampered by the immunogenicity of those molecules in patients. The development of molecular biology provides us with the opportunity to overcome the problem of immunogenicity and even allows the development of new immunotherapeutic approaches. These approaches use the MAb as carriers to deliver certain properties (MAb + X) to a specific site in the patient. These properties can be toxic principles like radioactivity or cytostatically active substances, enzymatic activities or specific receptor functions. In addition to the molecular biology of MAb a detailed analysis of the pharmacokinetic behaviour of molecules of MAb size (150 KD) and of small molecules (less than 1KD) in solid tissues gave rise to a new therapeutical concept called two phase immunotherapy. This concept is based on the separation of the localisation phase, the phase in which the MAb + X molecule localises at the position where therapy is desired, from the toxic phase. During the toxic phase, a untoxic "substance" develops a toxic activity by the action of the MAb + X only at the desired localisation. This concept is presently converted into practice in numerous different approaches, for example in a two phase tumor radioimmunotherapy, in a immune specific enzyme mediated chemotherapy (ISEC) and in a concept using Major Histocompatibility (MHC) antigen specific CTL as toxic agents to destroy MHC class I labeled target cells.