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High-Pressure Delivery of Oncolytic Viruses via Needle-Free Injection Preserves Therapeutic Activity
Aida Said1,2, Huy-Dung Hoang1,2, Nathalie Earl2
1Department of Biochemistry Microbiology and Immunology, 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.
Insights
Needle-free injection (NFI) effectively delivers oncolytic viruses (OVs) into tumors, showing comparable efficacy to traditional needle injections. This novel approach may enhance OV spread within tumors for improved virotherapy.
Area of Science:
- Oncolytic virotherapy
- Drug delivery systems
- Cancer research
Background:
- Intratumoral delivery of oncolytic viruses (OVs) for solid tumors typically relies on needle injections (NI).
- Limitations of NI include potential for needle-phobia and suboptimal viral distribution within the tumor microenvironment.
Purpose of the Study:
- To investigate needle-free injection (NFI) as a novel method for administering OVs to subcutaneous tumors.
- To assess the stability and efficacy of OVs delivered via NFI compared to NI.
Main Methods:
- In vitro evaluation of RNA and DNA virus stability and genetic integrity after exposure to high-pressure jet injectors.
- In vivo study using Vesicular Stomatitis Virus expressing luciferase (VSVΔ51-Luc) in a syngeneic CT26 subcutaneous tumor model.
- Comparison of viral dissemination, tumor growth reduction, and survival rates between NFI and NI delivery groups.
Main Results:
- Oncolytic viruses (OVs) maintained replication competence and infectivity after NFI, comparable to NI.
- NFI demonstrated successful delivery and enhanced dissemination of VSVΔ51-Luc within tumor tissues compared to NI.
- Tumor growth reduction and survival rates were similar between NFI and NI treated groups.
Conclusions:
- Needle-free injection (NFI) is a viable and effective approach for intratumoral delivery of oncolytic viruses (OVs).
- NFI may improve viral spread within accessible solid tumors, offering potential advantages for virotherapy.
- This study highlights NFI as a promising alternative delivery method in cancer treatment.
