High-Pressure Delivery of Oncolytic Viruses via Needle-Free Injection Preserves Therapeutic Activity

Author:

Said Aida12,Hoang Huy-Dung12,Earl Nathalie2,Xiang Xiao12ORCID,Siddiqui Nadeem3,Côté Marceline14ORCID,Alain Tommy124ORCID

Affiliation:

1. Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada

2. Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada

3. Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada

4. Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada

Abstract

Intratumoural delivery of oncolytic viruses (OVs) to solid tumours is currently performed via multiple percutaneous methods of needle injections (NI). In this study, we investigated the potential use of a novel delivery approach, needle-free injection (NFI), to administer OVs to subcutaneous tumours. The stability and genetic integrity of several RNA and DNA viruses exposed to high-pressure jet injectors were first evaluated in vitro. We demonstrate that replication competence and infectivity of the viruses remained unchanged after NFI, as compared to traditional NI. Using the oncolytic Vesicular Stomatitis Virus expressing luciferase (VSVΔ51-Luc) in the syngeneic CT26 subcutaneous tumour model, we show that NFI administration not only successfully delivers infectious particles but also increases the dissemination of the virus within the tumour tissues when compared to NI. Furthermore, mice treated with VSVΔ51-Luc by NFI delivery showed similar reduction in tumour growth and survival compared to those with needle-administered virus. These results indicate that NFI represents a novel approach to administer and potentially increase the spread of OVs within accessible solid tumours, highlighting its usefulness in virotherapy.

Funder

Terry Fox Research Institute

Natural Sciences and Engineering Research Council

Cancer Research Society

Canadian Cancer Society Research Institute Innovation

Canadian Institute of Health Research

NuGen Medical Devices

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference41 articles.

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5. Oncolytic Viruses for Cancer Therapy: Barriers and Recent Advances;Zheng;Mol. Ther. Oncolytics,2019

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