Linomide and antibody-targeted superantigen therapy abolishes formation of liver metastases in mice.
Hematogenous spread of tumor cells and metastasis formation in the liver are insidious aspects of cancer progression and are not frequently amenable to curative treatment. We examined the effect of Linomide and antibody-targeted therapy against the formation of hepatic metastases in vivo. For this purpose, syngenic B16 melanoma cells transfected with GA733-2 (a human colon cancer cell surface antigen) were injected into a mesenteric vein of C57/Bl6 mice. To test bacterial superantigen (Sag) targeting for immunotherapy of liver metastases, we used genetically fused proteins consisting of SEA and a Fab moiety of a GA733-2 tumor-reactive antibody (C215Fab-SEA). Linomide dose-dependently reduced hepatic metastases, and at 300 mg/kg this reduction was more than 80%. Treatment with C215Fab-SEA decreased metastases formation by 49% and the combination of Linomide and C215Fab-SEA was found to completely abolish liver metastases (>99% reduction). Taken together, our novel data suggest that Linomide and antibody-targeted superantigen therapy individually markedly reduce and together abolish liver metastases. Considering that current therapy of hepatic metastases is mainly limited to surgical resection in a subgroup of patients, these findings indicate that Linomide alone or in combination with antibody-targeted superantigen may provide a novel approach against liver metastases.
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
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Liu
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Klintman
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Corbascio
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Ekberg
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Hedlund
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Forsberg
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Thorlacius
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D006801:Humans; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007140:Immunoglobulin Fab Fragments / Q000235:genetics; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000517:prevention & control* / Q000556:secondary; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D018089:Superantigens / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; D007140:Immunoglobulin Fab Fragments; D016169:Lymphocyte Function-Associated Antigen-1; D011993:Recombinant Fusion Proteins; D018089:Superantigens; C045282:roquinimex