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Adoptive T-Cell Immunotherapy

Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY,volume 391)

Abstract

Epstein-Barr virus (EBV) is associated with a range of malignancies involving B cells, T cells, natural killer (NK) cells, epithelial cells, and smooth muscle. All of these are associated with the latent life cycles of EBV, but the pattern of latency-associated viral antigens expressed in tumor cells depends on the type of tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and therapy for EBV-associated malignancies for more than two decades. EBVSTs have been most successful as prophylaxis and therapy for post-transplant lymphoproliferative disease (PTLD) , which expresses the full array of latent EBV antigens (type 3 latency), in hematopoietic stem-cell transplant (HSCT) recipients. While less effective, clinical studies have also demonstrated their therapeutic potential for PTLD post-solid organ transplant and for EBV-associated malignancies such as Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and nasopharyngeal carcinoma (NPC) that express a limited array of latent EBV antigens (type 2 latency). Several approaches are actively being pursued to improve the antitumor activity of EBVSTs including activation and expansion of T cells specific for the EBV antigens expressed in type 2 latency, genetic approaches to render EBVSTs resistant to the immunosuppressive tumor environment, and combination approaches with other immune-modulating modalities. Given the recent advances and renewed interest in cell therapy, we hope that EBVSTs will become an integral part of our treatment armamentarium against EBV-positive malignancies in the near-future.

Keywords

  • Immunotherapy
  • T‐Cell therapy
  • EBV
  • Gene transfer
  • Cancer

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Acknowledgements

We are grateful for the long-term support from the NIH (NCI, NHLBI), The Department of Defense, and The Leukemia and Lymphoma Society. We are also grateful to the foundations that have supported our research focused on EBV-associated malignancies including Alex’s Lemonade Stand Foundation, and the V Foundation. We thank the supporting faculty and staff of the Stem Cell Transplant Unit, Clinical Research Unit, and Cell Processing Laboratory at Texas Children’s Hospital and Houston Methodist Hospital. We also thank the patients who participated in our studies, and the parents who entrusted the care of their children to us.

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Gottschalk, S., Rooney, C.M. (2015). Adoptive T-Cell Immunotherapy. In: Münz, C. (eds) Epstein Barr Virus Volume 2. Current Topics in Microbiology and Immunology, vol 391. Springer, Cham. https://doi.org/10.1007/978-3-319-22834-1_15

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