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Production of a Diverse Repertoire of Human Antibodies in Genetically Engineered Mice

Since mouse monoclonal antibody technology was established by KOhler and Milstein in 1975 (13), mouse monoclonal antibodies with high affinity and specificity to desired targets have been applied not only to basic research but also to diagnostic and therapeutic use. However, they are severely restricted for clinical use because of their immunogenicity in humans and the resulting reduction in their efficacy and safety. Thus, various technologies to produce human monoclonal antibodies that would permit repeated administration without immunogenic and allergic responses have been developed to date. In this review, we summarize the technologies to produce human monoclonal antibodies developed by others and describe our technology, which allows us to make mice with full-length human immunoglobulin loci containing human variable (V), diversity (D), joining (J) and constant (C) region genes. We then discuss the possibility of production of human polyclonal antibodies in large animals such as sheep and cows.