Oncolytic recombinant herpes simplex virus for treatment of orthotopic liver tumors in nude mice

Abstract

Cell-specific, replicating viruses are being developed as a new class of oncolytic agents. A novel approach to viral gene therapy with the use of replication-competent herpes simplex virus has been described; G92A is a replication-competent, multimutant oncolytic herpes simplex virus (HSV) that has been evaluated for anticancer effects and selectivity in the treatment of subcutaneous tumors. G92A replicates efficiently in albumin-producing tumor cell lines but not in non-albumin-producing tumor cell lines, whereas both types are equally susceptible to a non-tissue-specific recombinant HSV, hrR3. In this study, we analyzed the antitumoral efficacy of a single intrasplenic G92A or hrR3 injection in nude mice. In vivo, G92A replicated well in liver xenografts of human albumin-producing hepatoma cells (Hep3B) but not in liver xenografts of a non-albumin-producing malignant colon tumor cell line (HT29), whereas hrR3 replicated well in both tumor types. G92A effectively and selectively replicated throughout liver tumors without apparent hepatotoxicity and inhibited tumor growth, leading to a significantly increased survival time. By monitoring lacZ histochemical staining, we determined the oncolytic potential of recombinant HSV against liver tumors. Our results indicate that G92A warrants further investigation as a clinical therapy against malignant liver tumors.