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Therapeutic Effect of Irreversible Electroporation in Combination with Poly-ICLC Adjuvant in Preclinical Models of Hepatocellular Carcinoma
Institution:1. Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain;2. Immunology and Immunotherapy Program, Center for Applied Medical Research, University of Navarra, Avenida Pío XII, 55, 31008, Pamplona, Spain;1. UNC/NCSU Joint Department of Biomedical Engineering, Chapel Hill, North Carolina;2. Departments of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina;3. Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina;4. Division of Radiation Physics, Department of Radiation Oncology, Stanford University Medical Center, Stanford, California;5. Division of Abdominal Transplantation, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina;1. Department of Radiology, Memorial Sloan–Kettering Cancer Center, New York, New York;2. Department of Surgery, Division of Urology, Memorial Sloan–Kettering Cancer Center, New York, New York;3. Laboratory of Comparative Pathology, Memorial Sloan–Kettering Cancer Center, New York, New York;4. Weill Cornell Medical College, New York, New York;5. The Rockefeller University, Weill Cornell Medicine, New York, New York;6. Department of Urology, Palo Alto Medical Foundation, Palo Alto, California;7. Tenon Hospital, Assistance Publique–Hôpitaux de Paris Pierre & Marie Curie University, Paris, France;8. Medical University of Graz, Graz, Austria;1. Department of Diagnostic and Interventional Radiology, RWTH Aachen University Hospital, Aachen, Germany;2. Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany;3. Department of Radiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 160-8582, Japan;1. Department of Radiology, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, The Rockefeller University, 444 East 68th Street, New York, NY 10065;2. Department of Surgery, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, The Rockefeller University, 444 East 68th Street, New York, NY 10065;3. Research Animal Resource Center, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, The Rockefeller University, 444 East 68th Street, New York, NY 10065;4. Laboratory of Comparative Pathology, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, The Rockefeller University, 444 East 68th Street, New York, NY 10065;5. Department of Radiology, Medical University of Graz, Graz, Austria;1. Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia;2. Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Blacksburg, Virginia;3. Department of Surgery, Division of HPB Surgery, Carolinas Medical Center, 1000 Blythe Boulevard, Charlotte, NC 28203;1. Department of Small Animal Clinical Sciences, Virginia–Maryland College of Veterinary Medicine, DSACS, Phase II, 205 Duck Pond Drive (0442), Blacksburg, VA 24061;2. Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, DSACS, Phase II, 205 Duck Pond Drive (0442), Blacksburg, VA 24061;3. Department of Biomedical Engineering and Mechanics, Virginia Tech University, Blacksburg, Virginia
Abstract:PurposeTo evaluate the therapeutic efficacy of irreversible electroporation (IRE) combined with the intratumoral injection of the immunogenic adjuvant poly-ICLC (polyinosinic-polycytidylic acid and poly-L-lysine, a dsRNA analog mimicking viral RNA) inmediately before IRE.Materials and MethodsMice and rabbits bearing hepatocellular carcinoma tumors (Hepa.129 and VX2 tumor models, respectively) were treated with IRE (2 pulses of 2500V), with poly-ICLC, or with IRE + poly-ICLC combination therapy. Tumor growth in mice was monitored using a digital caliper and by computed tomography in rabbits.ResultsIntratumoral administration of poly-ICLC immediately before IRE elicited shrinkage of Hepa.129 cell-derived tumors in 70% of mice, compared to 30% and 26% by poly-ICLC or IRE alone, respectively (P = .0004). This combined therapy induced the shrinkage of VX-2-based hepatocellular carcinoma tumors in 40% of rabbits, whereas no response was achieved by either individual treatment (P = .045). The combined therapy activated a systemic antitumor response able to inhibit the growth of other untreated tumors.ConclusionsIRE treatment, immediately preceded by the intratumoral administration of an immunogenic adjuvant such as poly-ICLC, might enhance the antitumor effect of the IRE procedure. This combination might facilitate the induction of a long-term systemic response to prevent tumor relapses and the appearance of metastases.
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