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  • Review Article
  • Published:

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

Nature Reviews Clinical Oncology volume 21, pages 709–724 (2024)Cite this article

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Abstract

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.

Key points

  • Viruses can contribute to the development of cancer via inflammation, disruption of the cell cycle by viral oncoproteins, direct integration into the genome, and genomic instability and are often required for the proliferation of malignant cells.

  • Virus-specific T cell (VST) therapies have demonstrated a favourable safety profile and can be manufactured from autologous, allogeneic donor and third-party sources.

  • Although historically costly and time-consuming to manufacture, novel rapid manufacturing techniques promise to reduce the costs of and increase accessibility to VST therapies.

  • VSTs targeting Epstein–Barr virus (EBV) have the most substantial evidence of efficacy, with few adverse events, leading to the first regulatory approval of VSTs for use in oncology practice.

  • Adoptive cell therapy has not yet achieved success in the treatment of all virus-associated cancers owing to multiple barriers, including the immunosuppressive tumour microenvironment, tumour heterogeneity and viral immune evasion mechanisms.

  • Combinatorial treatment strategies might expand the clinical utility of VST therapies.

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Fig. 1: Virus-associated oncogenesis.
Fig. 2: Manufacturing of VST therapies.

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Acknowledgements

The work of the authors is supported by the US National Institutes of Health National Cancer Institute (Award Numbers 5P01 CA148600-09 and 1P01 CA225618-01A1 to C.M.B.); a Leukaemia and Lymphoma Society Translational Research Program award (to C.M.B.); and a Hyundai Hope on Wheels Scholar Grant (to K.T.).

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Authors and Affiliations

  1. Center for Cancer and Immunology Research, Children’s National Hospital, Washington, DC, USA

    Keri Toner, Chase D. McCann & Catherine M. Bollard

  2. Department of Paediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Keri Toner, Chase D. McCann & Catherine M. Bollard

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K.T. and C.D.M. researched data for the article. All authors contributed substantially to discussions of content, wrote the article, and reviewed and/or edited the manuscript before submission.

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Correspondence to Catherine M. Bollard.

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Competing interests

C.M.B. is on the Board of Directors of Cabaletta Bio and is a scientific co-founder and scientific advisory board member of Catamaran Bio, holds stock in Repertoire Immune Medicines and Neximmune, and serves on the data and safety monitoring board of Swedish Orphan Biovitrum (Sobi). The other authors declare no competing interests.

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Toner, K., McCann, C.D. & Bollard, C.M. Applications of cell therapy in the treatment of virus-associated cancers. Nat Rev Clin Oncol 21, 709–724 (2024). https://doi.org/10.1038/s41571-024-00930-x

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