A heavy-chain grafted antibody that recognizes the tumor-associated TAG72 antigen.
Murine anti-TAG72 antibodies react with more than 85% of human colorectal, gastric and ovarian carcinomas. However, the therapeutic utility of murine antibodies in human is severely restricted by their immunogenicity. The construction of humanized antibodies can potentially circumvent this problem. The latter antibodies can be generated by grafting CDRs from a murine antibody onto human immunoglobulin FRs followed by combining the resultant product with human immunoglobulin constant regions. In this study, we constructed a heavy-chain humanized anti-TAG72 antibody that we designated hmM4. This was achieved by the transplantation of CDRs from the murine VH of the ccM4 antibody into FRs of the human myeloma protein NEWM. The humanized antibody hmM4 retained its binding reactivity for the TAG72 antigen as measured by ELISA and Western blotting analysis respectively. However, it showed considerably less immunoreactivity for the TAG72 antigen than the original chimeric antibody ccM4. These results indicate that the murine anti-TAG72 specificity can be grafted to human immunoglobulin, and that the choice of the human immunoglobulin framework for the grafted antibody may be critical in maintenance of the immunoreactivity.
Sha
Y
Y
Saskatoon Cancer Center, Department of Microbiology, University of Saskatchewan, Canada.
Xiang
J
J
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data
D000906:Antibodies; D000951:Antigens, Neoplasm; D006023:Glycoproteins; C047052:tumor-associated antigen 72