Reshaping a therapeutic CD4 antibody.
An immunosuppressive rat antibody (Campath-9) against human CD4 has been reshaped for use in the management of autoimmunity and the prevention of graft rejection. Two different forms of the reshaped antibody were produced that derive their heavy chain variable region framework sequences from the human myeloma proteins KOL or NEW. When compared to a chimeric form of the CD4 antibody, the avidity of the KOL-based reshaped antibody was only slightly reduced, whereas that of the NEW-based reshaped antibody was very poor. The successful reshaping to the KOL-based framework was by a procedure involving the grafting of human framework sequences onto the cloned rodent variable region by in vitro mutagenesis.
Gorman
S D
SD
Department of Pathology, University of Cambridge, United Kingdom.
Clark
M R
MR
Routledge
E G
EG
Cobbold
S P
SP
Waldmann
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use; D015551:Autoimmunity; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology*; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D006084:Graft Rejection; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009194:Myeloma Proteins / Q000737:chemistry; D051381:Rats; D014162:Transfection
D000906:Antibodies; D015704:CD4 Antigens; D004274:DNA, Recombinant; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D009194:Myeloma Proteins; D004247:DNA