J. Lasarte Sagastibelza, Pamplona, ES

Irreversible electroporation (IRE) is an ablation technique that induces non-immunogenic tumor cell-death. Indeed IRE doesn´t promote inflammation that might help to activate antitumor immunity and get better long-term control of tumor growth. The purpose was evaluate the therapeutic efficacy of IRE combined with an immunogenic adjuvant Poly-ICLC (dsRNA-analog mimicking viral RNA) to induce an antitumoral inmune-response after death of the electroporated cells.

Material and methods

Antitumor efficacy of IRE+Poly-ICLC was evaluated in models of hepatocarcinoma. Mice and rabbits bearing hepatocellular carcinoma tumors (Hepa. 129 and VX-2 tumor models respectively) were treated with IRE (two pulses of 2500V), with poly-ICLC, or with the combination IRE+Poly-ICLC. Tumor gorwth in mice was monitored using a digital caliper and by CT in rabbits. Histologic studies and statistical-analysis parametric (Student´s test and one-way ANOVA) and non-parametric (Mann-Whitney U and Kruskall-Wallis) were carried on.

Results

Intratumoral administration of Poly-ICLC 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=0.0004). This combined therapy induced the shrinkage of VX-2-based hepatocellular tumors in 40% of rabbits. No response was achieved in individual treaments (p=.045). The combined therapy activated a systemic antitumor response that inhibit the growth of non-treated tumors (abscopal effect). In two rabbits a complete response was achieved.

Conclusion

IRE treatment, immediately preceded by intratumoral administration of an immunogenc adjuvant (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 appearance of metastases.

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