Oncolytic Viral Therapy in Osteosarcoma

Abstract

Primary bone malignancies, including osteosarcoma (OS), are rare but aggressive. Current OS treatment, involving surgical resection and chemotherapy, has improved survival for non-metastatic cases but remains ineffective for recurrent or metastatic OS. Oncolytic viral therapy (OVT) is a promising alternative, using naturally occurring or genetically modified viruses to selectively target and lyse cancer cells and induce a robust immune response against remaining OS cells. Various oncolytic viruses (OVs), such as adenovirus, herpes simplex virus, and measles virus, have demonstrated efficacy in preclinical OS models. Combining OVT with other therapeutics, such as chemotherapy or immunotherapy, may further improve outcomes. Despite these advances, challenges in reliability of preclinical models, safety, delivery, and immune response must be addressed to optimize OVT for clinical use. Future research should focus on refining delivery methods, exploring combination treatments, and clinical trials to ensure OVT's efficacy and safety for OS. Overall, OVT represents a novel approach with the potential to drastically improve survival outcomes for patients with OS.

Keywords: oncolytic viral therapy; oncolytic viruses; osteosarcoma.

Figure 1

Proposed mechanism of action of OVT: oncolytic viruses selectively infect and lyse tumor cells, releasing damage-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs), tumor antigens, and cytokines. These molecules are recognized by members of the innate immune system, such as natural killer cells and antigen-presenting cells, and by members of the adaptive immune system, such as helper (CD4) and cytotoxic (CD8) T cells. This results in a robust immune response, leading to the infiltration of the tumor microenvironment by additional immune cells.