Canine Adipose-Derived Mesenchymal Stem Cells (cAdMSCs) as a "Trojan Horse" in Vaccinia Virus Mediated Oncolytic Therapy against Canine Soft Tissue Sarcomas.

Ivan Petrov,Ivaylo Gentschev,Stefan Arnhold,Aladar A. Szalay,Michele C. Klymiuk,Anna Vyalkova,Mohamed I. Elashry

doi:10.3390/v12070750

Abstract

Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a “Trojan horse” for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors.

Highlights

The use of oncolytic virus strains is a novel approach for the treatment of canine cancer patients.Several different oncolytic viruses (OVs) have successfully been tested in the treatment of canine tumors [1,2,3,4]
We found that infection with C1-opt1 at a MOI of 0.5 exhibited the strongest expression of FP635 in both CT1258 (Figure 2A) and STSA-1 cells (Figure 2B)
The highest viral titers were identified in primary tumors of canine adipose-derived mesenchymal stem cells (cAdMSCs)/C1-opt1-treated mice (Table 2)

Summary

Introduction

The use of oncolytic virus strains is a novel approach for the treatment of canine cancer patients. Several different oncolytic viruses (OVs) have successfully been tested in the treatment of canine tumors [1,2,3,4]. One of the most important criteria for successful cancer therapy is the ability of the oncolytic virus to overcome different components of the host immune system including neutralizing antibodies and complementing adaptive antiviral immune cells. In order to evade virus inactivation by these factors, several strategies have been investigated, one of which includes the use of carrier systems for delivery of the oncolytic viruses. Viruses 2020, 12, 750 and tumor cells [9], have successfully been utilized as carriers to deliver OVs to tumors. Virus coatings with biocompatible polymers such as silk-elastin-like protein [10], polyethylene glycol (PEG) [11], and serum proteins [12,13], showed minimal sequestration by the mononuclear phagocytic system in the liver and spleen

Methods

Results

Conclusion