Creating and engineering human antibodies for immunotherapy

Targeting in immunotherapy has traditionally been achieved by using monoclonal rodent antibodies. Despite gene engineering, there are many problems and limitations associated with the non-human origin, the targeting specificity and the binding strength of these molecules. Now these issues may be addressed in a more rational way, by designing and then shaping, in vitro, the desired human antibodies. This review addresses how this may be achieved by the selection of monoclonal human antibodies from phage display libraries and the engineering of affinity and specificity thereafter. Phage display of antibody fragments has allowed access to large collections of different phage antibodies, created by cloning antibody V-genes from B-cells. Antibodies against any type of antigen may be derived from such repertoires, by rounds of enrichment on antigen and re-amplification. This review presents the state of the art in rational antibody design and creation. It will highlight the strengths of this increasingly important field, which will aid in the generation of tailor-made targeting entities for immunotherapy. (C) 1998 Elsevier Science.