Abstract
Monoclonal antibodies (mAbs) can mediate antitumor effects by indirect mechanisms involving antiangiogenesis and up-regulation of the cellular immune response rather than by direct tumor cell destruction. From mAbs raised by immunization of rats with transformed murine endothelial cells, a mAb (EOL4G8) was selected for its ability to eradicate a fraction of established colon carcinomas that did not express the EOL4G8-recognized antigen. The antigen was found to be ICAM-2 (CD102). Antitumor effects of EOL4G8, which required a functional T-cell compartment, were abrogated by depletion of CD8(+) cells and correlated with antitumor CTL activity, whereas only a mild inhibition of angiogenesis was observed. Interestingly, we found that EOL4G8 acting on endothelial ICAM-2 markedly enhances leukotactic factor activity-1-independent adhesion of immature dendritic cells to endothelium-an effect that is at least in part mediated by DC-SIGN (CD209).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / immunology*
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / immunology*
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Cell Adhesion / immunology
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Cell Adhesion Molecules / immunology*
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Colonic Neoplasms / immunology*
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / therapy
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Dendritic Cells / cytology
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Dendritic Cells / immunology
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Endothelium / cytology
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Endothelium / immunology
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Female
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Humans
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Lectins / immunology
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Lectins, C-Type*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Sequence Data
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Neoplasm Transplantation
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Receptors, Cell Surface / immunology
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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T-Lymphocytes, Cytotoxic / immunology
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Up-Regulation
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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ICAM2 protein, human
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Lectins
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Lectins, C-Type
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Receptors, Cell Surface