Production of Interleukin-2 by EL4 Tumor Cells Induces Natural Killer Cell- and T-Cell-Mediated Immunity
Autor: | E. I. H. van der Voort, L. A. Gravestein, Maarten Zijlstra, C. J. M. Melief, M. J. W. Visseren, M. Koot, Wybe Martin Kast, H. J. Schoenmakers |
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Rok vydání: | 1994 |
Předmět: |
Cytotoxicity
Immunologic Male Interleukin 2 Cancer Research Thymoma medicine.medical_treatment Immunology Mice Nude chemical and pharmacologic phenomena Biology Recombinant Interleukin Lymphocyte Activation Natural killer cell Mice Immune system Tumor Cells Cultured medicine Animals Immunology and Allergy Cytotoxic T cell Pharmacology Vaccines Lymphokine-activated killer cell Gene Transfer Techniques Immunotherapy Natural killer T cell Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Interleukin-2 T-Lymphocytes Cytotoxic medicine.drug |
Zdroj: | Journal of Immunotherapy. 15:119-128 |
ISSN: | 1524-9557 |
Popis: | Systemic administration of recombinant interleukin (rIL)-2 to cancer patients has met with limited clinical success since, despite significant antitumor effects, its use is associated with severe toxicity. Local production of IL-2 by IL-2 gene transfected tumor cells in murine model systems has been reported to induce specific immunity--devoid of toxicity--to the parental non-IL-2-producing tumor cells. We now report enhanced resistance in nonimmunized mice to murine EL4 thymoma cells, producing murine IL-2 following gene transfer (EL4pIL-2). This effect is mediated by activated natural killer (NK) cells, since we observed the same effect in nude mice but not in NK-depleted mice. Additionally, in mice repeatedly vaccinated with irradiated EL4pIL-2 cells, we observed immunity to challenge with a tumorigenic dose of EL4 cells transfected with a control vector, EL4p. EL4-specific cytotoxic T-lymphocytes (CTLs) were detected in these mice. Mice vaccinated with irradiated EL4p cells were less protected against challenge with a tumorigenic dose of EL4p cells. This study indicates that although some IL-2-producing autologous tumor cells elicit NK-mediated responses and not CTL responses upon inoculation, tumor-specific CTL responses are generated upon repeated vaccinations with these cells. This strategy has potential application for treating a wide variety of cancer patients with autologous IL-2 producing tumor cells. |
Databáze: | OpenAIRE |
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