Neoadjuvant treatment of hepatic malignancy: an oncolytic herpes simplex virus expressing IL-12 effectively treats the parent tumor and protects against recurrence-after resection

摘要: The objective of the study was to evaluate utility NV1042, a replication competent, oncolytic herpes simplex virus (HSV) containing interleukin-12 (IL-12) gene, as primary treatment for hepatic tumors and further assess its ability reduce tumor recurrence following resection. Resection is most effective therapy malignancies, but not possible in majority patients. Furthermore, common after resection, often remnant liver likely because microscopic residual disease setting postoperative host cellular immune dysfunction. We hypothesize that, unlike other gene transfer approaches, direct injection with HSV expressing IL-12 will only provide control parent tumor, also elicit an response directed at cells, thus decreasing risk cancer Solitary Morris hepatomas, established Buffalo rat livers, were injected directly 10(7) particles NV1023, identical NV1042 without or saline. Following injection, resected measured animals challenged intraportal 10(5) recreating clinical scenario cancer. In vitro cytotoxicity against hepatoma cells similar both viruses multiplicity infection 1 (MOI, ratio viral target cells), >90% cell kill by day 6. induced high-level expression vitro, peaking 4 days culture. single intratumoral marked interferon-gamma (IFN-gamma) expression. Both significant local evidenced increase number CD4(+) CD8(+) lymphocytes, although peak infiltration later compared NV1023. NV1023 reduced volume 74% (P<.003) 52% (P<.03), respectively, animals. Treatment significantly resection rechallenge (16.8+/-11 (median=4) vs. 65.9+/-15 (median=66) animals, P<.025). conclusion, combined stimulation offers protects ease use this modality approach, which appears be superior either approach alone, suggests that it may have relevance, patients unresectable neoadjuvant strategy reducing