Revolutionizing cancer treatment with oncolytic viruses: From tumor targeting and metabolic reprogramming to immune activation and precision delivery

Oncolytic viruses (OVs) have emerged as promising immunotherapeutic agents capable of selectively killing tumor cells while saving healthy tissues. Advances in genetic engineering have enhanced OV efficacy by embracing immune-stimulating molecules, like GM-CSF and combining them with other treatments such as checkpoint inhibitors. Beyond direct oncolysis, OVs induce immunogenic cell death and release tumor-associated antigens that activate dendritic cells and cytotoxic T lymphocytes, thus boosting antitumor immunity. Despite their potential, challenges such as limited intra-tumoral penetration, immune evasion and rapid clearance remain significant barriers. New delivery strategies including nanoparticle encapsulation, mesenchymal stem cell carriers and vesicle-based systems are under observation to improve stability and targeting. Personalized approaches that align OV therapy with unique tumor profiles may further enhance therapeutic success. Overcoming these hurdles could strongly establish oncolytic virotherapy as an evolutionary approach in cancer immunotherapy and underscoring the need for continued research and well-designed clinical trials to fully recognize its potential.