Reza Ghavimi, Leila Rahimian, Mohsen Mohammadi, Ojasvi Dutta, Harikrishnan Mohan, Vladimir N. Chouljenko, Tolulope O. Omolekan, Jean Christopher Chamcheu, Konstantin G. Kousoulas
vaccine that educates the immune system. Moreover, OVs directly trigger both innate and adaptive immunity and can be genetically engineered to secrete immune-boosting factors. Early studies have shown promising synergistic antitumor effects when OVs are combined with other cancer therapies or immunotherapies. A key advantage of OVs is their capacity to reprogram the tumor microenvironment (TME), transforming immunologically inert "cold" tumors into actively inflamed "hot" tumors. This environmental shift is crucial for successful immunotherapy, as it allows for increased infiltration of immune cells, particularly cytotoxic T lymphocytes (CTLs), into the tumor. This comprehensive review covers the history, mechanisms, and potential combinatorial strategies involving OVs. It also addresses the challenges faced in their development and highlights current clinical trials exploring their role as potent immunotherapeutic agents.