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Giving Oncolytic Viruses a Free Ride: Carrier Cells for Oncolytic Virotherapy
Alberto Reale1, Arianna Calistri1, Jennifer Altomonte2
1Department of Molecular Medicine, University of Padua, 35121 Padua, Italy.
Abstract:
Oncolytic viruses (OVs) are an emerging class of therapeutics which combine multiple mechanisms of action, including direct cancer cell-killing, immunotherapy and gene therapy. A growing number of clinical trials have indicated that OVs have an excellent safety profile and provide some degree of efficacy, but to date only a single OV drug, HSV-1 talimogene laherparepvec (T-Vec), has achieved marketing approval in the US and Europe. An important issue to consider in order to accelerate the clinical advancement of OV agents is the development of an effective delivery system. Currently, the most commonly employed OV delivery route is intratumoral; however, to target metastatic diseases and tumors that cannot be directly accessed, it is of great interest to develop effective approaches for the systemic delivery of OVs, such as the use of carrier cells. In general, the ideal carrier cell should have a tropism towards the tumor microenvironment (TME), and it must be susceptible to OV infection but remain viable long enough to allow migration and finally release of the OV within the tumor bed. Mesenchymal stem cells (MSCs) have been heavily investigated as carrier cells due to their inherent tumor tropism, in spite of some disadvantages in biodistribution. This review focuses on the other promising candidate carrier cells under development and discusses their interaction with specific OVs and future research lines.
Insights
Oncolytic viruses (OVs) show promise for cancer treatment. Developing effective systemic delivery systems, particularly using novel carrier cells beyond mesenchymal stem cells (MSCs), is crucial for advancing OV therapies.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Gene therapy
Background:
- Oncolytic viruses (OVs) are emerging therapeutics with direct tumor-killing, immunotherapeutic, and gene therapy mechanisms.
- While OVs show efficacy and safety, only one has gained market approval, highlighting the need for improved delivery systems.
- Intratumoral delivery is common, but systemic delivery is essential for metastatic and inaccessible tumors.
Purpose of the Study:
- To review promising carrier cell candidates for systemic oncolytic virus delivery.
- To discuss the interaction between specific OVs and alternative carrier cells.
- To identify future research directions for OV delivery systems.
Main Methods:
- Review of current literature on oncolytic virus delivery systems.
- Analysis of carrier cell properties, including tumor tropism and OV interaction.
- Discussion of mesenchymal stem cells (MSCs) and other potential carrier cells.
Main Results:
- Mesenchymal stem cells (MSCs) are investigated for OV delivery due to tumor tropism but have biodistribution limitations.
- Alternative carrier cells are being developed to overcome MSC limitations for effective systemic OV delivery.
- The ideal carrier cell must target the tumor microenvironment (TME), support OV replication, and facilitate OV release within the tumor.
Conclusions:
- Effective systemic delivery is key to advancing oncolytic virus therapy.
- Exploring novel carrier cells beyond MSCs is critical for overcoming current delivery challenges.
- Further research into carrier cell-OV interactions will optimize oncolytic virus treatment strategies.
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