Laboratory InvestigationTherapeutic Effect of Irreversible Electroporation in Combination with Poly-ICLC Adjuvant in Preclinical Models of Hepatocellular Carcinoma
Section snippets
Materials and Methods
This study was approved by the Institutional Animal Care and Use Committee (Ref. 111-15). and conformed to U.S. National Institutes of Health guidelines for the humane handling of laboratory animals.
Therapeutic Effect of IRE in Combination with a Poly-ICLC Adjuvant in a Murine Model for HCC
Mice bearing Hepa-129 tumors (>5 mm in diameter) were randomly divided into different experimental groups (n = 10–17; see Materials and Methods section) and treated with: (i) IRE (n = 15), (ii) intratumoral injection of poly-ICLC (n = 10), (iii) intratumoral injection of poly-ICLC immediately followed by IRE (n = 17), or (iv) left untreated (tumor growth control group) (n = 12). It was found that, while treatment of mice with IRE alone or poly-ICLC alone induced tumor shrinkage in 26.6% and 30%
Discussion
Clinical trials have shown that IRE is safe but still inefficient for long-term control of disease 5, 20, 21. This long-term control could be achieved if an immune response against the tumor was elicited. IRE produces cellular destruction causing the release of a substantial amount of tumor-specific antigens that can be engulfed by dendritic cells (DCs) for their presentation to tumor-specific T lymphocytes. The efficient priming of these T lymphocytes is only achieved when DCs are at a mature
Acknowledgments
The study was supported by grants from PIUNA Universidad de Navarra, FIMA, Ministerio de Economia y Competitividad (SAF2016-78568-R), “Murchante se mueve contra el cancer” and Fundación Bancaria La Caixa-Hepacare Project.
We thank Elena Ciordia, Gloria Abizanda, Igor Alkain, and Alberto Espinal for excellent animal care; Andoni Fourco for helping in the design of electrodes for the IRE system; and Mikel Ariz and Laura Guembe for the histologic analyses. We also thank Dr. Andres Salazar for
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None of the authors have identified a conflict of interest.