1. Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs.
- Author
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Green LL, Hardy MC, Maynard-Currie CE, Tsuda H, Louie DM, Mendez MJ, Abderrahim H, Noguchi M, Smith DH, Zeng Y, David NE, Sasai H, Garza D, Brenner DG, Hales JF, McGuinness RP, Capon DJ, Klapholz S, and Jakobovits A
- Subjects
- Adult, Age Factors, Amino Acid Sequence, Animals, Antibodies, Monoclonal biosynthesis, Antibodies, Monoclonal genetics, Antibody Formation, Base Sequence, Humans, Hybridomas immunology, Immunoglobulin kappa-Chains biosynthesis, Immunoglobulin mu-Chains biosynthesis, Mice, Molecular Sequence Data, Recombinant Fusion Proteins immunology, Sequence Alignment, Species Specificity, Tetanus Toxin immunology, Tetanus Toxoid biosynthesis, Tetanus Toxoid immunology, Antibodies, Monoclonal immunology, Chromosomes, Artificial, Yeast, Genes, Immunoglobulin, Immunoglobulin kappa-Chains genetics, Immunoglobulin mu-Chains genetics, Mice, Transgenic immunology, Recombinant Fusion Proteins biosynthesis
- Abstract
We describe a strategy for producing human monoclonal antibodies in mice by introducing large segments of the human heavy and kappa light chain loci contained on yeast artificial chromosomes into the mouse germline. Such mice produce a diverse repertoire of human heavy and light chains, and upon immunization with tetanus toxin have been used to derive antigen-specific, fully human monoclonal antibodies. Breeding such animals with mice engineered by gene targeting to be deficient in mouse immunoglobulin (Ig) production has led to a mouse strain in which high levels of antibodies are produced, mostly comprised of both human heavy and light chains. These strains should provide insight into the adoptive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential.
- Published
- 1994
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