title: Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs.
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.
authors.affiliation: Cell Genesys, Inc., Foster City, California 94404.
authors.forename: L L
authors.initials: LL
authors.lastname: Green
authors.forename: M C
authors.initials: MC
authors.lastname: Hardy
authors.forename: C E
authors.initials: CE
authors.lastname: Maynard-Currie
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: D M
authors.initials: DM
authors.lastname: Louie
authors.forename: M J
authors.initials: MJ
authors.lastname: Mendez
authors.forename: H
authors.initials: H
authors.lastname: Abderrahim
authors.forename: M
authors.initials: M
authors.lastname: Noguchi
authors.forename: D H
authors.initials: DH
authors.lastname: Smith
authors.forename: Y
authors.initials: Y
authors.lastname: Zeng
authors.forename: N E
authors.initials: NE
authors.lastname: David
authors.forename: H
authors.initials: H
authors.lastname: Sasai
authors.forename: D
authors.initials: D
authors.lastname: Garza
authors.forename: D G
authors.initials: DG
authors.lastname: Brenner
authors.forename: J F
authors.initials: JF
authors.lastname: Hales
authors.forename: R P
authors.initials: RP
authors.lastname: McGuinness
authors.forename: D J
authors.initials: DJ
authors.lastname: Capon
authors.forename: S
authors.initials: S
authors.lastname: Klapholz
authors.forename: A
authors.initials: A
authors.lastname: Jakobovits
mesh_terms: D000328:Adult; D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000917:Antibody Formation; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast; D005803:Genes, Immunoglobulin; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000276:immunology; D016415:Sequence Alignment; D013045:Species Specificity; D013744:Tetanus Toxin / Q000276:immunology; D013745:Tetanus Toxoid / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D013745:Tetanus Toxoid