Oncolytic Virus Therapy in Solid Tumors: Clinical Translation Challenges and Strategies

Oncolytic viruses (OVs), as a type of tumor-targeted immunotherapy, show great potential in solid tumor treatment by selectively infecting and lysing tumor cells, while activating the host's anti-tumor immune response. Although products like H101 and T-VEC have been approved, their clinical translation still faces a core dilemma: feasibility of the mechanism does not equal clinical efficacy. Currently, the clinical translation of oncolytic viruses faces three major challenges. First, the preclinical-to-clinical translation dilemma, as existing animal models are unable to accurately predict the replication efficiency and immune response of the virus in the human body; second, the challenges at the clinical development stage, due to the lack of effective biomarkers to guide patient selection; and third, delivery and pharmacokinetics issues, where intratumoral injection is only suitable for superficial tumors, while systemic administration faces dual barriers from immune and physical obstacles in the tumor microenvironment. To address these challenges, the article proposes corresponding optimization strategies: first, optimizing viral vectors to enhance virus targeting and immune evasion capabilities; second, upgrading delivery systems to achieve systemic targeted delivery of the virus; and third, optimizing dosing regimens and combination therapies to induce immunogenic cell death and improve the tumor microenvironment. In the future, with advancements in precision medicine and delivery technologies, oncolytic virus therapy is expected to bring new breakthroughs in solid tumor treatment.