TY - JOUR
T1 - Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system
T2 - Mannan-binding protein-dependent cell-mediated cytotoxicity
AU - Ma, Yong
AU - Uemura, Kazuhide
AU - Oka, Shogo
AU - Kozutsumi, Yasunori
AU - Kawasaki, Nobuko
AU - Kawasaki, Toshisuke
PY - 1999/1/19
Y1 - 1999/1/19
N2 - Mannan-binding protein (MBP), a Ca2+-dependent mammalian lectin specific for mannose and N-acetylglucosamine, is an important serum component associated with innate immunity. MBP activates complement and functions as a direct opsonin on binding to mannooligosaccharide-bearing pathogens. We have found that MBP recognizes and binds specifically to oligosaccharide ligands expressed on the surfaces of a human colorectal carcinoma. Interestingly, the recombinant vaccinia virus carrying human MBP gene was demonstrated to possess a potent growth-inhibiting activity against human colorectal carcinoma cells transplanted in KSN nude mice when administered by intra- tumoral or subcutaneous injection. Moreover, a significant prolongation of life span of tumor-bearing mice resulted from the treatment. This effect appears to be a consequence of local production of MBP. Unexpectedly, the mutant MBP, which had essentially no complement-activating activity, was nearly as active as wild-type MBP. These results indicated that MBP has a previously undescribed cytotoxic activity, which we propose to term MBP- dependent cell-mediated cytotoxicity(MDCC). In addition, this study provides a model for the development of an effective and specific host defense factor for cancer gene therapy.
AB - Mannan-binding protein (MBP), a Ca2+-dependent mammalian lectin specific for mannose and N-acetylglucosamine, is an important serum component associated with innate immunity. MBP activates complement and functions as a direct opsonin on binding to mannooligosaccharide-bearing pathogens. We have found that MBP recognizes and binds specifically to oligosaccharide ligands expressed on the surfaces of a human colorectal carcinoma. Interestingly, the recombinant vaccinia virus carrying human MBP gene was demonstrated to possess a potent growth-inhibiting activity against human colorectal carcinoma cells transplanted in KSN nude mice when administered by intra- tumoral or subcutaneous injection. Moreover, a significant prolongation of life span of tumor-bearing mice resulted from the treatment. This effect appears to be a consequence of local production of MBP. Unexpectedly, the mutant MBP, which had essentially no complement-activating activity, was nearly as active as wild-type MBP. These results indicated that MBP has a previously undescribed cytotoxic activity, which we propose to term MBP- dependent cell-mediated cytotoxicity(MDCC). In addition, this study provides a model for the development of an effective and specific host defense factor for cancer gene therapy.
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U2 - 10.1073/pnas.96.2.371
DO - 10.1073/pnas.96.2.371
M3 - Article
C2 - 9892640
AN - SCOPUS:0033582313
SN - 0027-8424
VL - 96
SP - 371
EP - 375
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 2
ER -