Therapeutic Effect of Irreversible Electroporation in Combination with Poly-ICLC Adjuvant in Preclinical Models of Hepatocellular Carcinoma
Vivas I (1), Iribarren K (2), Lozano T (2), Cano D (1), Lasarte-Cia A (2), Chocarro S (2), Gorraiz M (2), Sarobe P (2), Hervás-Stubbs S (2), Bilbao JI (1), Casares N (3), Lasarte JJ (2).
(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.
(3) Immunology and Immunotherapy Program, Center for Applied Medical Research, University of Navarra, Avenida Pío XII, 55, 31008, Pamplona, Spain.
To 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 METHODS:
Mice 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.
Intratumoral 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.
IRE 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.
CITA DEL ARTÍCULO J Vasc Interv Radiol. 2019 May 14. pii: S1051-0443(19)30290-8. doi: 10.1016/j.jvir.2019.02.023