Establishment and characterization of mouse-human chimeric monoclonal antibody to erbB-2 product.
A mouse-human chimeric antibody for erbB-2 product was established by a new procedure using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The E401 hybridoma secreted anti-erbB-2 product monoclonal antibody (MoAb) (IgG1, kappa). The gene of the mouse variable regions of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the E401 hybridoma RNA. The variable region of heavy chain was joined with the expression vector, which contains human gamma 1 constant gene. The expression vector was transfected into heavy chain loss mutant cells E401-12, which produced only murine immunoglobulin light chains. A chimeric monoclonal antibody CH401 retained full binding reactivity to erbB-2 product, compared with murine E401 parental antibody. Furthermore, the chimeric MoAb CH401 was much more efficient in supporting antibody dependent cell-mediated cytotoxicity activity against erbB-2-bearing human adenocarcinoma cells than murine MoAb E401. These suggest that a chimeric monoclonal antibody CH401 may be a potent reagent for therapy of human adenocarcinomas.
Ishida
T
T
Department of Internal Medicine (Section 1), Sapporo Medical University.
Tsujisaki
M
M
Hinoda
Y
Y
Imai
K
K
Yachi
A
A
D000230:Adenocarcinoma / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D017931:DNA Primers; D066246:ErbB Receptors / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D000922:Immunotoxins / Q000096:biosynthesis*; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D017931:DNA Primers; D066246:ErbB Receptors; D007143:Immunoglobulin Heavy Chains; D000922:Immunotoxins; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins