Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system: Mannan-binding protein-dependent cell-mediated cytotoxicity

Yong Ma, Kazuhide Uemura, Shogo Oka, Yasunori Kozutsumi, Nobuko Kawasaki, Toshisuke Kawasaki

Research output: Contribution to journalArticlepeer-review

128 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)371-375
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number2
DOIs
Publication statusPublished - 19-01-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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