A Comprehensive Review of Modern Cancer Therapies Utilizing Oncolytic Viruses

Oncolytic viruses (OVs) are gaining traction as advanced tools in cancer therapy. They are distinguished by their ability to destroy malignant cells while sparing normal tissue specifically. In addition to their direct tumor-lysing properties, an essential benefit of oncolytic virus therapy is its capacity to activate both the innate and adaptive immune systems. To enhance these therapeutic actions, many OVs have been genetically engineered to encode immune-modulating factors that reestablish or strengthen antitumor immune responses. Recent studies show that combining OVs with other forms of immunotherapy—such as immune checkpoint inhibitors, CAR-T cells, specific T-cell receptor therapies, or autologous tumor-infiltrating lymphocytes—offers significant advances in cancer treatment. This article reviews how OVs work, discusses strategies to enhance their immunogenicity further, and presents the latest rational combinations of oncolytic viruses with other immunotherapies based on current preclinical and clinical research.