Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs.
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.
Green
L L
LL
Cell Genesys, Inc., Foster City, California 94404.
Hardy
M C
MC
Maynard-Currie
C E
CE
Tsuda
H
H
Louie
D M
DM
Mendez
M J
MJ
Abderrahim
H
H
Noguchi
M
M
Smith
D H
DH
Zeng
Y
Y
David
N E
NE
Sasai
H
H
Garza
D
D
Brenner
D G
DG
Hales
J F
JF
McGuinness
R P
RP
Capon
D J
DJ
Klapholz
S
S
Jakobovits
A
A
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
D000911:Antibodies, Monoclonal; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D013745:Tetanus Toxoid