Applications of cell therapy in the treatment of virus-associated cancers

A diverse range of viruses have well-established roles as the primary driver of oncogenesis in various haematological malignancies and solid tumours. Indeed, estimates suggest that approximately 1.5 million patients annually are diagnosed with virus-related cancers. The predominant human oncoviruses include Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B and C viruses (HBV and HCV), human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV1), and Merkel cell polyomavirus (MCPyV). In addition, although not inherently oncogenic, human immunodeficiency virus (HIV) is associated with immunosuppression that contributes to the development of AIDS-defining cancers (specifically, Kaposi sarcoma, aggressive B cell non-Hodgkin lymphoma and cervical cancer). Given that an adaptive T cell-mediated immune response is crucial for the control of viral infections, increasing research is being focused on evaluating virus-specific T cell therapies for the treatment of virus-associated cancers. In this Review, we briefly outline the roles of viruses in the pathogenesis of these malignancies before describing progress to date in the field of virus-specific T cell therapy and evaluating the potential utility of these therapies to treat or possibly even prevent virus-related malignancies. Several different viruses have a role in cancer pathogenesis, contributing to the development of various haematological malignancies and solid tumours via diverse, multifaceted mechanisms. However, this viral aetiology presents a unique opportunity for adoptive virus-specific T cell (VST) therapy. This Review summarizes the mechanisms of viral carcinogenesis and describes the current clinical experience with adoptive cellular immunotherapies for virus-related cancers, predominantly using non-genetically modified VSTs. The authors also discuss challenges and future directions for the ongoing clinical development of VST therapies.