Efeito oncolítico da cepa vacinal La Sota do vírus da doença de Newcastle em neoplasias mamárias e prostáticas: Análises em modelos in vitro, in ovo e in vivo

Abstract

Since the 1950s, the oncolytic capacity of Newcastle disease virus (NDV) has been reported, and it is currently recognized as an alternative and complementary medicine. Since then, several studies have demonstrated the therapeutic potential of wild-type and recombinant strains of avian Paramyxovirus type 1, either as monotherapy or in combination with other treatments, with oncolytic effects observed both in vitro and in humans and animal models. In veterinary oncology, mammary tumors are the most frequently diagnosed neoplasms in female dogs and present a high malignancy rate. However, few studies have evaluated the oncolytic effects of the La Sota strain of NDV on canine mammary tumors. The present study was divided into three chapters. The first addressed general considerations. The second chapter investigated the oncolytic efficacy of the La Sota strain of NDV on human prostate adenocarcinoma PC-3 cells and its ex ovo effects on PC-3 cell xenografts, analyzing inhibition, regression, angiogenesis, and cytokine release. The results indicated a dose-dependent reduction in PC-3 tumor cell viability, without significantly affecting normal cells, as well as inhibition of xenograft tumor growth in the chorioallantoic membrane (CAM) model. The third chapter focused on the oncolytic efficacy of the La Sota strain of NDV on CMT-U27 canine mammary carcinoma cells and the in vivo therapeutic impact of intravenous virus administration in female dogs with spontaneous mammary carcinomas. The findings demonstrated a dose-dependent reduction in CMT-U27 tumor cell viability without significantly affecting normal cells. In the clinical trial, three female dogs received three intravenous NDV infusions, resulting in manageable adverse events. Treatment response was heterogeneous: one dog showed disease stabilization, while two experienced tumor progression, suggesting that individual factors influenced the effectiveness of virotherapy. Additionally, IgG antibodies against the virus were detected in two patients, indicating immune activation. Although preliminary, these findings underscore the need for more structured therapeutic protocols and studies involving larger animal cohorts and combination therapies, suggesting that NDV may represent an innovative and promising approach for the treatment of mammary neoplasms in dogs, contributing to the advancement of veterinary oncology.