Biodistribution Analysis of Oncolytic Adenoviruses in Canine Patient Necropsy Samples Treated with Cellular Virotherapy

Abstract

Oncolytic immunotherapy with competent viruses is an emerging approach in cancer treatment. The clinical safety of many types of oncolytic viruses (OVs) has been demonstrated. However, there is a lack of information about viral bio distribution in patients. The available data about oncolytic adenovirus biodistribution in human subjects treated intrave nously consists of virus detection in body fluids, a few tumor biopsies, and a single report of patient necropsy samples. There is no information about adenoviral biodistribution in patients treated intravenously with cellular vehicles carrying an onco lytic adenovirus. We previously published reports regarding the efficacy and clinical safety of infusing mesenchymal stem cells (MSCs) infected with an OV in human and canine pa tients. In this study, we performed necropsies on 12 canine pa tients treated with dCelyvir, canine MSCs infected with ICO CAV17, a canine oncolytic adenovirus. The prevalence of microscopic lesions, especially chronic inflammatory responses in different organs, was higher than expected. Concomitantly, we found a positive immunoreaction to ICOCAV17 in analyzed samples. These findings support a possible role of the virus in development of histopathological alterations and ongoing systemic viral replication of ICOCAV17 in the period after therapy administration