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Immunotherapy of intraperitoneal cancer with interleukin 2 and lymphokine-activated killer cells reduces tumor load and prolongs survival in murine models
Authors:R T Ottow  E P Steller  P H Sugarbaker  R A Wesley  S A Rosenberg
Affiliation:1. The Surgery Branch, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, and Cedis Laboratory, Bethesda, Maryland 20892 USA;2. Biostatistics, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, and Cedis Laboratory, Bethesda, Maryland 20892 USA;3. Data Management Section, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, and Cedis Laboratory, Bethesda, Maryland 20892 USA;1. Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands;2. GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands;3. Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;4. Divisions of Diagnostic Oncology and Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;5. Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands;1. Department of Surgical Oncology, Catharina Cancer Institute, Michelangelolaan 2, 5623 EJ, Eindhoven, Netherlands;2. Department of Research and Development, Netherlands Comprehensive Cancer Organization, Godebaldkwartier 319, 3511 DT, Utrecht, Netherlands;3. Department of Medical Oncology, Catharina Cancer Institute, Michelangelolaan 2, 5623, Eindhoven, Netherlands;4. Department of Surgical Oncology, Erasmus Medical Center, Doctor Molewaterplein 40, 3015, Rotterdam, Netherlands;5. GROW – School for Oncology and Developmental Biology, Maastricht University, Universiteitssingel 40, 6229, Maastricht, Netherlands;1. Department of Gynecology, The Netherlands Cancer Institute, Amsterdam, the Netherlands;2. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands;3. Center for Gynecologic Oncology Amsterdam, Amsterdam, the Netherlands;4. Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands;5. Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, the Netherlands;6. Department of Obstetrics & Gynecology, Sint Antonius Hospital, Nieuwegein, the Netherlands;7. Department of Gynecological Oncology, UMC Utrecht Cancer Center, Utrecht, the Netherlands;8. Department of Gynecology and Obstetrics, Catharina Hospital, Eindhoven, the Netherlands;9. Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands;10. The Dutch Peritoneal Oncology Group, the Netherlands;11. Department of Obstetrics and Gynecology, Amsterdam University Medical Center, Amsterdam, the Netherlands;12. Department of Gynecological Oncology, University Medical Center Groningen, Groningen, the Netherlands;13. Department of Gynecological Oncology, Radboud University Medical Center, Nijmegen, the Netherlands;14. Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands;15. Department of Surgery, Aarhus University Hospital, Aarhus, Denmark;p. Department of Pathology, University Hospital Ghent, Ghent, Belgium;q. Dutch Gynecological Oncology Group, the Netherlands;1. Department of Surgery, Meander Medical Centre, Amersfoort, Netherlands;2. Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands;3. Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands;4. Department of Surgery, Atrium Medical Centre, Heerlen, Netherlands;5. Department of Surgery, Ikazia Hospital, Rotterdam, Netherlands;6. Department of Surgery, Jeroen Bosch Hospital, Den Bosch, Netherlands
Abstract:The control of malignancy disseminated within the peritoneal cavity is an important problem in the management of low-grade gastrointestinal and ovarian neoplasms. A model of peritoneal carcinomatosis in the mouse was used to investigate the potential of lymphokine-activated killer (LAK) cells and exogenous interleukin 2 (IL-2) to control intraperitoneal tumor. LAK cells are splenocytes activated in vitro by IL-2. C57BL/6 mice were injected intraperitoneally with a lethal inoculum of syngeneic MCA-105 tumor. Three days later, the established tumor was treated with adoptively transferred LAK cells and/or exogenous IL-2 administration. LAK cells alone were ineffective in reducing intraperitoneal tumor. Administration of IL-2 alone resulted in limited tumor reduction. Treatment with exogenous IL-2 in conjunction with LAK cells resulted in the greatest reduction of intraperitoneal tumor. The larger the number of LAK cells given, the greater the reduction in tumor. Frequent intraperitoneal bolus administration of IL-2 was more effective than a single daily intraperitoneal injection and intraperitoneal administration of IL-2 and LAK was more effective than systemic treatments. Marked prolongation of life was seen in mice treated with LAK cells plus exogenous IL-2. We conclude that intraperitoneal LAK cells plus exogenous IL-2 is an effective treatment regimen for reducing intraperitoneal tumor in this murine model.
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