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Published on: December 3, 2013
Biodistribution Analysis of Oncolytic Adenoviruses in Canine Patient Necropsy Samples Treated with Cellular
Ana Gómez1, David Sardón1, Teresa Cejalvo2
1Veterinary Pathology Unit, Universidad Alfonso X el Sabio, 28691 Madrid, Spain.
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 biodistribution in patients. The available data about oncolytic adenovirus biodistribution in human subjects treated intravenously 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 oncolytic 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 patients. In this study, we performed necropsies on 12 canine patients treated with dCelyvir, canine MSCs infected with ICOCAV17, 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.
Insights
Oncolytic virus therapy using mesenchymal stem cells (MSCs) showed unexpected lesions in canine patients. Further research is needed to understand the long-term effects and viral replication of oncolytic adenoviruses delivered via cellular vehicles.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Viral biodistribution
Background:
- Oncolytic viruses (OVs) are promising cancer therapeutics, with demonstrated clinical safety.
- Information on OV biodistribution, especially adenoviruses delivered via cellular vehicles, remains limited in humans.
- Previous studies showed efficacy and safety of OV-infected mesenchymal stem cells (MSCs) in humans and canines.
Purpose of the Study:
- To investigate the biodistribution and potential histopathological effects of canine oncolytic adenovirus (ICOCAV17) delivered via canine MSCs (dCelyvir).
- To assess viral replication and associated lesions in canine patients post-treatment.
Main Methods:
- Necropsies were performed on 12 canine patients treated with dCelyvir (canine MSCs infected with ICOCAV17).
- Microscopic examination of various organs for lesions, particularly chronic inflammatory responses.
- Immunoreaction analysis to detect the presence of ICOCAV17 in tissue samples.
Main Results:
- A higher-than-expected prevalence of microscopic lesions, including chronic inflammatory responses, was observed in multiple organs.
- A positive immunoreaction to ICOCAV17 was detected in analyzed tissue samples.
- Findings suggest potential histopathological alterations linked to the virus and ongoing systemic viral replication.
Conclusions:
- The study indicates a possible role for ICOCAV17 in causing histopathological changes in treated canines.
- Evidence of ongoing systemic viral replication of ICOCAV17 was found post-therapy.
- Further investigation into the long-term biodistribution and safety of OV-loaded cellular vehicles is warranted.
