Preparation of genetically engineered monoclonal antibodies for human immunotherapy

Abstract

Production of human monoclonal antibodies (MAbs) of predefined specificity using conventional hybridoma technology has proved to be difficult. Immunotherapeutic intervention in humans with rodent MAbs, however, is disadvantageous because of the antigenicity of these proteins and may result in human antibody responses against this foreign agent. To circumvent this problem, recombinant DNA techniques have been developed to transplant the specificity of a rodent MAb into a human antibody. Two basic approaches are being employed: first, combining rodent MAb variable regions with human constant regions; and more recently, “reshaping” human MAbs by grafting complementarity-determining regions (CDR) into the human antibody framework. These humanized MAbs can now be used to study human Fc-dependent effector mechanisms in detail, which seems essential to optimize potential in vivo application.