Virus-Specific T Cells for the Immunocompromised Patient
Open Access
- 11 October 2017
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 8, 1272
- https://doi.org/10.3389/fimmu.2017.01272
Abstract
While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant (HSCT) offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease (GVHD). Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but confer protection in 70-90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naïve or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naïve donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo.Keywords
Funding Information
- National Institutes of Health (PO1 CA148600)
This publication has 96 references indexed in Scilit:
- Transferred WT1-Reactive CD8 + T Cells Can Mediate Antileukemic Activity and Persist in Post-Transplant PatientsScience Translational Medicine, 2013
- Adoptive Immunotherapy With CMV-specific Cytotoxic T Lymphocytes for Stem Cell Transplant Patients With Refractory CMV InfectionsJournal of Immunotherapy, 2012
- Selectively T Cell-Depleted Allografts from HLA-Matched Sibling Donors Followed by Low-Dose Posttransplantation Immunosuppression to Improve Transplantation Outcome in Patients with Hematologic MalignanciesTransplantation and Cellular Therapy, 2011
- Inducible Apoptosis as a Safety Switch for Adoptive Cell TherapyNew England Journal of Medicine, 2011
- How I treat EBV lymphoproliferationBlood, 2009
- Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global PerspectiveTransplantation and Cellular Therapy, 2009
- Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopesBlood, 2009
- Immunobiology of Human Cytomegalovirus: from Bench to BedsideClinical Microbiology Reviews, 2009
- Antitumor Activity of EBV-specific T Lymphocytes Transduced With a Dominant Negative TGF-β ReceptorJournal of Immunotherapy, 2008
- Safe adoptive transfer of virus‐specific T‐cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantationBritish Journal of Haematology, 2006