Oncolytic Viruses: From Basics to Challenges to Innovation

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Abstract
The landscape of cancer therapeutics has undergone a transformative shift from broad approaches, such as radiation and chemotherapy, to more precise strategies, encompassing small molecule kinase inhibitors and monoclonal antibodies targeting immune checkpoint molecules. Oncolytic viruses (OVs) have recently emerged as a promising and viable option for cancer immunotherapy, particularly for “cold” tumors entrenched in an immunologically-suppressive tumor microenvironment. Genetic attenuation refines the characteristics of OVs, replacing specific genes to enhance conditional viral replication within tumor cells. Despite their potential, the therapeutic use of OVs faces challenges such as pre-mature elimination by the immune system of the host alongside the dense stromal barriers. In this review article, the strategic encapsulation of genetically-engineered OVs within intra-lesional/-tumoral carriers/ vehicles such as mesenchymal stem cells are explored. To further enhance vector delivery strategies and precise targeting, protecting/shielding OVs from host immune responses, via utilizing release-controlled nanoparticles and employing nanofilaments to optimize vector propagation, for example, are discussed. Such innovative approaches not only mitigate challenges related to pre-mature viral clearance and stromal barriers yet also facilitates a localized, controlled, and sustained release of OVs, thereby optimizing their therapeutic bio-safety and -impact. Ongoing clinical investigations are exploring the synergies between OVs and carriers/delivery systems, combined with various anti-cancer therapeutics as radiotherapy, chemotherapy, immune checkpoint inhibitors, and monoclonal antibodies. These studies hold promise for revolutionizing cancer treatment, ensuring both safety and efficacy, aiming to advance bio-pharmaceutical delivery systems from bench-top to bed-side for enhanced therapeutic results, improved patient survival, and enhanced quality of life or QoL.

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