ABSTRACT
This chapter discusses the status of humanized monoclonal antibodies (MoAbs) having potential clinical relevance and the biochemical and molecular biological approaches used to generate these recombinant biomolecules. The immunogenicity of MoAbs of nonhuman origin generally precludes their repeated administration in immunodiagnostic and immunotherapeutic clinical protocols. The chapter reviews the salient molecular approaches which were utilized to generate these humanized MoAbs, and discusses their resulting immunogenicities, especially with regard to clinical applications. Antibody modeling in these applications has taken many forms, ranging from visual inspection of the deduced sequences and comparisons to consensus sequences to sophisticated computerized algorithms, including modeling by homology, energy minimization, as well as by combined approaches. The potential immunogenicity of the murine complementarity-determining regions, in the context of the humanized MoAb, is considered from the standpoint of structural elements which may be especially accessible for inducing anti-idiotypic responses.
