Artikel: Redirected cellular cytotoxicity by infection of effector cells with a recombinant vaccinia virus encoding a tumor-specific monoclonal antibody.
2000 Band 7, Heft 4, Seite(n) 615–623
Abstract: Cytotoxicity is an important function of the immune system that results in the destruction of cellular targets by humoral and/or cellular mechanisms. We wanted to assess the possibility of targeting the lytic function of immune cells toward cancer cells, ...
Abstract | Cytotoxicity is an important function of the immune system that results in the destruction of cellular targets by humoral and/or cellular mechanisms. We wanted to assess the possibility of targeting the lytic function of immune cells toward cancer cells, which express the gene coding for a known tumor antigen (Ag) (GA733-2/epithelial cell adhesion molecule), using a viral vector encoding a monoclonal antibody (mAb) specific for said tumor Ag (CO17-1A). To this end, we have constructed recombinant vaccinia viruses expressing the sequences corresponding to mAb CO17-1A, which recognizes a specific Ag (GA733-2) that is present on the surface of most gastrointestinal carcinomas. The recombinant vectors encoding either a secreted or membrane-anchored form of CO17-1A mAb were used to infect effector cells, which were subsequently assessed for their cytotoxic activity. The recombinant viruses were able to infect both granulocyte-macrophage colony-stimulating factor-activated human macrophages and Ag-stimulated murine cytotoxic T lymphocytes. Infected granulocyte-macrophage colony-stimulating factor-activated macrophages were found to be able to kill GA733-2-expressing tumor cells. Likewise, infected cytotoxic T lymphocytes, although conserving their original alloreactivity, gained the capability of killing GA733-2-expressing cancer cells. |
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Mesh-Begriff(e) | Animals ; Antibodies, Monoclonal/genetics ; Antigens, Neoplasm/immunology ; Biomarkers, Tumor/immunology ; Cell Adhesion Molecules/immunology ; Cells, Cultured ; Cytotoxicity, Immunologic ; Epithelial Cell Adhesion Molecule ; Genetic Vectors ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Light Chains/genetics ; Macrophages/immunology ; Mast-Cell Sarcoma ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/biosynthesis ; Spleen/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Tumor Cells, Cultured ; Vaccinia virus/genetics |
Chemische Substanzen | Antibodies, Monoclonal ; Antigens, Neoplasm ; Biomarkers, Tumor ; Cell Adhesion Molecules ; Epithelial Cell Adhesion Molecule ; Immunoglobulin Heavy Chains ; Immunoglobulin Light Chains ; Recombinant Proteins |
Sprache | Englisch |
Erscheinungsdatum | 2000-04 |
Erscheinungsland | England |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 1212513-1 |
ISSN | 0929-1903 |
ISSN | 0929-1903 |
DOI | 10.1038/sj.cgt.7700161 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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