Derivation of Therapeutically Active Humanized and Veneered Anti-CD18 Antibodies

The identification and production of murine monoclonal antibodies (MAbs) has led to numerous therapeutic applications of these exquisitely specific molecules to human disease. The technologies of molecular biology have further expanded the utility of many antibodies by allowing the creation of class-switched molecules, whose functionality has been improved by the acquisition or loss of complement fixation. The size of the bioactive molecule may also be reduced so as to increase the tissue target availability of the antibody, either by changing the class from an IgM to an IgG, removing most of the heavy chain constant region in the creation of a F(ab′)2, or severely truncating both heavy and light chain constant regions with the formation of an Fv antibody. Common to all of these potentially therapeutic forms of antibody are the requisite CDRs (complementarity-determining regions), which guide the molecule to its ligand, and the framework residues (FRs), which support the latter structures and dictate the disposition of the CDRs relative to one another.