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Oncolytic virotherapy has emerged as a novel form of cancer immunotherapy. Oncolytic viruses (OVs) can directly infect and lyse the tumor cells, and modulate the beneficial immune microenvironment. Vaccinia virus (VACV) is a promising oncolytic vector because of its high safety, easy gene editing, and tumor intrinsic selectivity. To further improve the safety, tumor-targeting ability, and OV-induced cancer-specific immune activation, various approaches have been used to modify OVs. The recombinant oncolytic VACVs with deleting viral virulence factors and/or arming various therapeutic genes have displayed better therapeutic effects in multiple tumor models. Moreover, the combination of OVs with other cancer immunotherapeutic approaches, such as immune checkpoint inhibitors and CAR-T cells, has the potential to improve the outcome in cancer patients. This will open up new possibilities for the application of OVs in cancer treatment, especially for personalized cancer therapies.

Design Strategies and Precautions for Using Vaccinia Virus in Tumor Virotherapy