Anaplastic Thyroid Cancer (ATC) is one of the most aggressive human malignancies with a median survival of six months and a fatal prognosis. ATC is notoriously resistant to conventional therapy and as such, novel therapies are needed. This study evaluates the efficacy of the recombinant herpes oncolytic virus NV1023 in a murine orthotopic model.
Material and Methods
NV1023 is an attenuated, replication-competent mutant of HSV-1. The ATC cell line DRO90-1 was transfected with constitutively expressed Renilla luciferase and is designated RLucDRO90-1. Nude mice underwent direct intrathyroidal injection with 1e6 RLucDRO90-1 cells. After 13 days, mice were randomized to receive treatment with intratumoral NV1023 or saline. Tumor progression was followed using serial bioluminescence imaging and tumor volumes were measured at autopsy.
Results
RLucDRO90-1 tumors grew rapidly and reliably in the murine thyroid with local tracheal invasion. Bioluminescence imaging allowed for non-invasive tracking of tumor burden. Tumor fluorescence intensity was significantly decreased for animals in the NV1023 treated group. Average fluorescence intensity was 68200 units in the virally treated group and 221800 units in the saline treated group at day 23 of the study (P<0.05). Average tumor volumes were 1229.44 mm3 (� 727.67) and 151.93 mm3 (� 55.15) in the saline and virally treated groups respectively at autopsy (P<0.05).
Conclusions
RLucDRO90-1 is a novel, stably transfected cell line that grows reliably and invasively in an orthotopic murine model of ATC, and allows for non-invasive in vivo monitoring of tumor burden. Intratumoral injection of NV1023 effectively treated ATC in this model.