Investigation of oncolytic effect of recombinant Newcastle disease virus in primary and metastatic oral melanoma

Abstract

AbstractMalignant melanoma is aggressive cancer with a high rate of local invasiveness and metastasis. Currently, the treatment options for patients with advanced-stage and metastatic oral melanoma are limited. A promising treatment option is oncolytic viral therapy. This study aimed to evaluate novel therapies for malignant melanoma using a canine model. Oral melanoma, which frequently occurs in dogs is used as a model for human melanoma, was isolated and cultured and used for the evaluation of the tumor lytic effect induced by viral infection. We constructed a recombinant Newcastle disease virus (rNDV) that promotes the extracellular release of IFNγ from the virus-infected melanoma. The expression of oncolytic and apoptosis-related genes, the immune response by lymphocytes, and IFNγ expression were evaluated in virus-infected melanoma cells. The results showed that the rate of rNDV infection varied according to the isolated melanoma cells and the oncolytic effect differed between melanoma cells owing to the infectivity of the virus. The oncolytic effect tended to be greater for the IFNγ-expressing virus than for the GFP-expressing prototype virus. Additionally, lymphocytes co-cultured with the virus showed induced expression of Th1 cytokines. Therefore, recombinant NDV expressing IFNγ is expected to induce cellular immunity and oncolytic activity. This oncolytic treatment shows promise as a therapeutic approach for melanoma treatment once evaluated using clinical samples from humans.