Production and characterization of a mouse/human chimeric antibody directed against human neuroblastoma.
Hybridoma CE7 produces a murine antibody (gamma 1/kappa) which binds to a 190-kDa cell-surface glycoprotein of human neuroblastoma. Because of its tumor specificity, it has been used routinely in clinical pathology to confirm diagnosis of neuroblastoma. We have isolated the gene segments coding for the variable regions of the immunoglobulin H and L chain of this hybridoma. These V genes were used to construct mouse/human chimeric H and L chain genes (gamma 1/kappa) which were then expressed in SP2/0 cells. A cell-binding inhibition assay showed that the specificity of the chimeric CE7 antibody (chCE7) is identical to that of the original CE7. Radioiodinated chCE7 binds to approximately 43,000 sites per neuroblastoma cell with an affinity of 10(10) M-1. In neuroblastoma-bearing nude mice, biodistribution studies with [125I]chCE7 were performed and tumor accumulations of up to 32% of injected dose/g tissue together with low blood and organ uptake were found.
Amstutz
H
H
Central Laboratory, Blood Transfusion Service of the Swiss Red Cross, Bern.
Rytz
C
C
Novak-Hofer
I
I
Spycher
M
M
Schubiger
P A
PA
Blaser
K
K
Morgenthaler
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D000918:Antibody Specificity; D001483:Base Sequence; D001665:Binding Sites; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015342:DNA Probes; D015698:Genomic Library; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003176:Complement C3; D003181:Complement C4; D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region