Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression.
MoAbs against tumour-associated antigens (TAA) may be useful for the treatment of colorectal cancer. Since an increased expression of TAA may lead to enhanced antibody-dependent cellular cytotoxicity we examined whether the cytokines IL-2, IL-4, IL-6, IL-10, IL-12, interferon-alpha (IFN-alpha), IFN-gamma, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and tumour necrosis factor-alpha can influence EpCAM and LewisY expression on the surface of the colorectal carcinoma cell lines HT29, LoVo and SW480. We found that only IFN-alpha increased significantly whereas IL-4 decreased both EpCAM and LewisY expression. IFN-gamma significantly increased LewisY expression only. When tumour cells were treated with MoAb, the LewisY-specific MoAb BR55-2 down-regulated LewisY antigen expression, whereas MoAb 17-1A, which binds to EpCAM, up-regulated this TAA after 3 days of culture. The cytokines IFN-alpha or IFN-gamma combined with MoAb 17-1A enhanced further slightly the expression of EpCAM. In additional experiments with chemotherapeutic drugs commonly used for the treatment of colorectal cancer, we found that 5-fluorouracil, mitomycin-C and oxaliplatin up-regulated EpCAM and LewisY antigen expression. Raltitrexed enhanced LewisY and down-regulated EpCAM expression, whereas CPT-11 had no influence at all. The highest expression for EpCAM on HT29 cells was achieved by the combination of IFN-alpha, 5-fluorouracil and MoAb 17-1A. Our results may be useful for defining combinations of biological and chemotherapeutic drugs for the treatment of colorectal cancer. Further trials should evaluate to what extent these combinations enhance antibody-dependent cellular cytotoxicity.
Flieger
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Medizinische Klinik und Poliklinik I, Allgemeine Innere Medizin, Universität Bonn, Bonn, Germany. D. Flieger@uni-bonn.de
Hoff
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Sauerbruch
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Schmidt-Wolf
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D000276:Adjuvants, Immunologic / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D000071858:Epithelial Cell Adhesion Molecule; D005472:Fluorouracil / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D007372:Interferons / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D000077146:Irinotecan; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis* / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D016685:Mitomycin / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011799:Quinazolines / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000071858:Epithelial Cell Adhesion Molecule; D007378:Interleukins; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; D000077150:Oxaliplatin; D016685:Mitomycin; D000077146:Irinotecan; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007372:Interferons; C068874:raltitrexed; D005472:Fluorouracil; D002166:Camptothecin