Repurposing licensed viral vaccines as anti-cancer therapeutics: Turning cold tumors hot

Rising cancer incidences worldwide underline the need for effective and globally accessible therapies. Oncolytic viruses (OV), targeting tumor cells and stimulating anti-tumor immunity, are attractive anti-cancer agents but face challenges like stringent regulatory hurdles and excessive costs, which decelerate their global clinical implementation. Licensed viral vaccines for cancer therapy have emerged as a promising alternative to OVs, leveraging their well-established safety profiles and potential cost benefits. This review discusses the current understanding on their anti-cancer effects. Preclinical experiments, case studies and clinical trials highlight their anti-cancer potential and reveal underlying mechanisms. Similar to OVs, viral vaccines can transform "cold" tumor immune microenvironments into "hot," synergize with immune checkpoint inhibitors, and are not necessarily hampered by pre-existing immunity. Collectively, they represent a promising and readily available addition to cancer therapy. Further studies into optimizing efficacy, delivery, and synergy, as well as clinical evaluation are warranted to fully realize their anti-cancer potential.