Lymphokine-activated killer cytotoxicity against pancreas adenocarcinoma cell lines and vascular endothelial cells

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Abstract
Eight pancreas carcinoma cell lines of duct cell origin (PCI‐6, 10, 19, 24, 35, 43, 55, and 64) were established. Using one of these lines, PCI‐24, human umbilical vein endothelial cells (HUVEC), and several recombinant cytokines, conditions and specificity of antl‐PCI LAK induction were Investigated, with the focus on a search for lymphokine‐activated killer (LAK) activity that differentiates neoplastic (PCI) from non‐neoplastic (HUVEC) cells. Interferon‐γ (IFN‐γ), IFN‐α, IL‐4, 11–6, and IL‐7, but not tumor necrosis factor‐α (TNF‐α) or IL‐1β, induced a weak LAK activity against PCI‐24, whereas IL‐2‐induced (1000U/mL) LAK exhibited a far more potent cytotoxicity. When these cytokines were added at the suboptimal dose IL‐2 (100U/mL), no significant augmentation in LAK activity was induced. Staphylococcal protein A (SpA) induced LAK activity as potent as that seen with IL‐2 (1000 U/mL). Both IL‐2‐induced and SpA‐induced LAK had a potent, dose‐dependent cytotoxicity against HUVEC. HUVEC inhibited both IL‐2– and SpA‐induced LAK cytotoxicity against PCI‐24 to almost the same extent as seen with PCI‐24. Thus, two potent LAK‐inducers did not generate LAK activity that differentiates neoplastic from non‐neoplastic cells. Thus, in vitro cytotoxicity of LAK agalnst non‐neoplastic endothelial cells is unavoidable when handling cytokines in LAK induction.