Evaluation of the effect in vivo and vitro of a new therapy based on Newcastle disease virus (NDV) in a transplantable canine cancer model

Vincristine is an effective therapy for the treatment of canine transmissible venereal tumor (CTVT); however, the time for a complete clinical remission may vary depending on the tumor stage and host status. The aim of this study was to investigate an alternative or adjuvant therapy usingNewcastledisease virus (NDV) for the treatment of CTVT that does not produce side effects and enhances the immune response against the tumor.

Each of five dogs (1 male/4 females, median age = 6 years, median body-weight = 15.5 kg) from an suburban area of Chincha (Ica, Peru), diagnosed with CTVT by microscopy, were weekly injected with 2.5x10⁸ copies/mL of a velogenic strain of NDV from turkey, directly into the tumor. The tumor size was calculated through the formula [length x width x height x π/4(cm3)] and evaluated for 5 weeks. CTVT cells, obtained from tumor biopsies, were cultured during 11 days and then infected in vitro with NDV at multiplicity of infection (MOI)=1. At 4 days post-infection (dpi); the NDV viral load, as well as the apoptosis and late apoptosis/necrosis, were evaluated by real time PCR and flow cytometry, respectively.

At the start of the treatment, the tumor size ranged from 2.5 to 567.5 cm³; five weeks after, a decrease in the tumor size between 25%-99% was observed among the patients without occurrence of adverse symptoms. 3/5 patients had a tumor reduction greater than 50%. At 4 dpi in vitro, a significant increase of apoptosis (median = 13.5%) and late apoptosis/necrosis (median = 21.6%) was observed in infected CTVT cells compared to uninfected CTVT cells (median=6.0% and median=4.8%; respectively, P < 0.05). A median NDV viral load of 5x10⁷ copies/mL was observed in infected CTVT cells.

Our results suggest that NDV is able to replicate into CTVT cells, directly inhibiting tumor cell growth by inducing apoptosis/necrosis in vivo and in vitro.