Metastatic neuroendocrine
cancer still constitutes a palliative situation, lacking promising treatment options.
Oncolytic virotherapy, a novel type of virus-based
immunotherapy, lyses
tumor cells using genetically engineered viruses thereby activating the immune system to induce an optimized antitumor response which could bring down
tumor masses to a stage of minimal
residual tumor disease. The oncolytic vector
talimogene laherparepvec (
T-VEC, herpes simplex virus [HSV] type 1) has already shown excellent safety profiles in clinical studies and has become the first ever FDA/EMA-approved oncolytic virus (OV). This work presents a first preclinical assessment of this state-of-the-art OV, using a panel of human
neuroendocrine tumor/
neuroendocrine carcinoma (NET/NEC) cell lines. Cytotoxicity, transgene expression, and viral replication patterns were studied. Furthermore, the antiproliferative activity was compared to the one of mTOR inhibitor
Everolimus and also interactions between the OV and
Everolimus were evaluated. Moreover, virostatic effects of
ganciclovir (GCV) on replication of
T-VEC were assessed and electron microscopic pictures were taken to comprehend viral envelopment and details of the replication cycle of
T-VEC in human neuroendocrine
cancer. It could be shown that
T-VEC infects, replicates in, and lyses human NET/NEC cells exhibiting high oncolytic efficiencies already at quite low virus concentrations. Interestingly,
Everolimus was not found to have any relevant impact on rates of viral replication, but no additive effects could be proved using a combinatorial
therapy regimen. On the other hand, GCV was shown to be able to limit replication of
T-VEC, thus establishing an important safety feature for future treatments of NET/NEC patients. Taken together,
T-VEC opens up a promising novel treatment option for NET/NEC patients, warranting its further preclinical and clinical development.