Oncogenic viral antigens for engineered T cell immunotherapy: Challenges and opportunities

Viruses that cause malignancies such as hepatocellular carcinoma and cervical cancer are the cause of approximately 20% of all human cancers. In recent years, engineered T cell immunotherapy targeting tumor‐associated antigens (TAAs) has had some success against virus‐associated cancer, although these treatments are associated with side effects. TAA‐specific‐modified T cells may kill cancer cells but they also react with and damage healthy tissue. During an oncogenic virus infection, viral DNA integrates into the host genome, leading to the expression of viral‐specific antigens in the tumor in a restricted and durable manner. The cross‐reactive side‐effects of conventional TAA‐specific engineered T cell treatment can be avoided by creating engineered T cells that target oncogenic viral antigens. To chart a course for the discovery of additional viral‐specific antigens and their combination with immune checkpoint inhibition therapies, this review summarizes the development, preclinical research, and clinical application of oncogenic viral antigen–specific T cell immunotherapy. This review also addresses challenges such as virus mutation and diverse integration, which can result in the loss of the target.