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Virus-Specific T Cells for the Treatment of Malignancies—Then, Now, and the Future

  • Preclinical and Clinical Cellular Therapies (E Horwitz, Section Editor)
  • Published:
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Abstract

Purpose of Review

Virus-associated malignancies are a global health burden, constituting 10–12% of cancers worldwide. As these tumors express foreign viral antigens that can elicit specific T cell responses, virus-directed immunotherapies are a promising treatment strategy. Specifically, adoptive cell transfer of virus-specific T cells (VSTs) has demonstrated the potential to eradicate cancers associated with certain viruses.

Recent Findings

Initial studies in 1990s first showed that VSTs targeting the Epstein-Barr virus (EBVSTs) can induce complete remissions in patients with EBV-induced post-transplant lymphoproliferative disease. Since then, studies have validated the specificity and safety of VSTs in some lymphomas and solid malignancies. However, challenges remain to optimize this platform for widespread use, including enhancing potency and persistence, overcoming the immunosuppressive tumor microenvironment, and streamlining manufacturing processes that comply with regulatory requirements.

Summary

This review focuses on data from clinical trials evaluating VSTs directed against three viruses (EBV, HPV, and MCPyV), as well as recent preclinical and clinical advances, and potential future directions.

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Acknowledgments

S. Sharma is supported by CPRIT RP160283 - Baylor College of Medicine Comprehensive Cancer Training Program grant and NIH grants NIH-NCI P50 CA 126752 - SPORE in Lymphoma and FCCICF - NCI Cancer Center Support Grant P30CA16672. W.K. Leung is supported by a Genesis Oncology Trust Murray Jackson Clinical Fellowship and a HSANZ New Investigator Scholarship. H.E. Heslop is supported by NIH grants PO1 CA94237, P50CA12675, a Specialized Center of Research Award from the Leukemia Lymphoma Society, the Dan L Duncan Cancer Canter support grant P30CA125123.

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  1. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital, Houston, TX, USA

    Sandhya Sharma, Wingchi K Leung & Helen E Heslop

  2. Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Sandhya Sharma

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HEH has ownership interest (including stock, patents, etc.) in Allovir and Marker Therapeutics, and is a consultant/advisory board member for Novartis, Gilead Biosciences, Kiadis, and PACT Pharma and has received commercial research grants from Cell Medica and Tessa Therapeutics. SS and WL have no potential conflicts of interest.

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Sharma, S., Leung, W.K. & Heslop, H.E. Virus-Specific T Cells for the Treatment of Malignancies—Then, Now, and the Future. Curr Stem Cell Rep 6, 17–29 (2020). https://doi.org/10.1007/s40778-020-00170-6

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