Metal-binding chimeric antibodies expressed in Escherichia coli.
Metallothionein, a well-characterized biological chelator of metals, has been genetically fused to the binding domain of an antibody and expressed in the periplasm of Escherichia coli. Specific delivery of 109Cd to immobilized hapten or to haptenated cells was demonstrated directly in periplasmic extracts. This approach is potentially useful for targeted radiotherapy and diagnostic imaging. We find six to seven atoms of metal per active antigen-combining site. Absence of the Fc portion of the immunoglobulin along with low immunogenicity of metallothionein-metal complexes should reduce immunologic reactions.
Sawyer
J R
JR
Department of Genetics, University of Wisconsin, Madison 53703.
Tucker
P W
PW
Blattner
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001483:Base Sequence; D002106:Cadmium Radioisotopes / Q000378:metabolism; D004926:Escherichia coli; D015870:Gene Expression; D006241:Haptens / Q000378:metabolism; D008546:Melanoma, Experimental; D008668:Metallothionein / Q000737:chemistry*; D008969:Molecular Sequence Data; D009592:Nitrohydroxyiodophenylacetate; D011877:Radionuclide Imaging / Q000379:methods; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002106:Cadmium Radioisotopes; D006241:Haptens; D011993:Recombinant Fusion Proteins; D009592:Nitrohydroxyiodophenylacetate; D008668:Metallothionein