Therapeutic Effect of Irreversible Electroporation in Combination with Poly-ICLC Adjuvant in Preclinical Models of Hepatocellular Carcinoma

J Vasc Interv Radiol. 2019 Jul;30(7):1098-1105. doi: 10.1016/j.jvir.2019.02.023. Epub 2019 May 14.

Abstract

Purpose: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Carboxymethylcellulose Sodium / administration & dosage
  • Carboxymethylcellulose Sodium / analogs & derivatives*
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Electroporation / methods*
  • Injections, Intralesional
  • Liver Neoplasms, Experimental / immunology
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / therapy*
  • Mice, Inbred C3H
  • Poly I-C / administration & dosage*
  • Polylysine / administration & dosage
  • Polylysine / analogs & derivatives*
  • Rabbits
  • Tumor Burden

Substances

  • Adjuvants, Immunologic
  • Polylysine
  • poly ICLC
  • Carboxymethylcellulose Sodium
  • Poly I-C