Chimerization of Mu-9: a colon-specific antigen-p antibody reactive with gastrointestinal carcinomas.
BACKGROUND
Mu-9 is a murine monoclonal antibody that is directed against affinity-purified colon-specific antigen-p (CSAp). CSAp is a tumor-associated antigen that is present in 60% of colorectal carcinomas. Preclinical and clinical studies have shown Mu-9 to have excellent targeting abilities. However, as administration of the murine immunoglobulin G (IgG) provoked a human anti-mouse antibody response, chimerization of Mu-9 is warranted for decreasing immunogenicity.


METHODS
Polymerase chain reaction and cDNA library screening methods were used for the cloning of Mu-9 heavy and light chain variable regions for the construction of chimeric Mu-9.


RESULTS
The functional chimeric Mu-9 antibody binds to the CSAp antigen in the GW-39 extracts. It has immunochemical properties similar to that of murine Mu-9.


CONCLUSIONS
The V-region sequence information will be used for design of humanized Mu-9, which will be evaluated for targeting gastrointestinal carcinomas.
Krishnan
I S
IS
Immunomedics, Inc., Morris Plains, New Jersey 07950, USA.
Hansen
H J
HJ
Losman
M J
MJ
Goldenberg
D M
DM
Leung
S O
SO
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001483:Base Sequence; D005770:Gastrointestinal Neoplasms / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins; C030139:colon-specific antigen