Targeted killing of cancer cells is the future of cancer treatment, an approach that results in better outcomes and fewer side-effects. Numerous different mechanisms to target and destroy specific types of cell have been developed in recent years, and one of these involves the use of natural or engineered viruses that preferentially attack cancer cells:
Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity.
With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy.
OVs provide a number of potential advantages as cancer vaccines over conventional therapies. First, OVs are tumor-selective, thus in situ cancer vaccines, providing higher cancer specificity and better safety margin. Second, immunogenic/inflammatory types of cell death, including recently characterized "immunogenic cell death" (ICD) of cancer and stromal cells induced by OVs provides a natural repertoire of tumor-associated antigens (TAAs) in conjunction with danger signals to elicit anti-tumor immunity.