Establishment and Operation of a Third-Party Virus-Specific T Cell Bank within an Allogeneic Stem Cell Transplant Program

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Barbara WithersDavid J Gottlieb

Abstract

Hematopoietic stem cell transplantation (HSCT) donor-generated virus-specific T cells (VSTs) can provide effective treatment for viral infection post-HSCT but are not readily accessible to all patients. Off-the-shelf cryopreserved VSTs suitable for treatment of multiple patients are an attractive alternative. We generated a bank of 17 cytomegalovirus (CMV)-, 14 Epstein-Barr virus (EBV)-, and 15 adenovirus (AdV)-specific T cell products from 30 third-party donors. Donors were selected for expression of 6 core HLA antigens expressed at high frequency in the local transplant population. T cells were generated by co-culturing venous blood or mobilized hematopoietic stem cell (HSC)-derived mononuclear cells with monocyte-derived dendritic cells pulsed with overlapping peptides covering CMV pp65, AdV5 hexon, or EBV BZLF1/LMP2A/EBNA1 proteins. Addition of a CD14+ selection step instead of plate adherence to isolate monocytes before culture initiation significantly improved expansion in cultures from HSC material. Phenotyping showed the CD8+ subset to have significantly higher numbers of terminal effector T cells (CD45RA+62L-) and lower numbers of effector memory T cells (CD45RA-62L-) when compared with the CD4+ subset. Increased expre...Continue Reading

Citations

Oct 9, 2019·Current Opinion in Oncology·Gaurav Sutrave, David J Gottlieb
Aug 5, 2020·Expert Review of Hematology·Mi KwonJosé Luis Díez-Martín
Apr 3, 2020·Journal of Translational Medicine·Nele Carolin HeinemannBritta Eiz-Vesper
Jun 23, 2019·Current Hematologic Malignancy Reports·Wei JiangEmily Blyth
Feb 8, 2019·Journal of Hematology & Oncology·Theresa KaeuferleTobias Feuchtinger
Dec 1, 2020·Expert Opinion on Biological Therapy·Lorna Neill, Karl Peggs
Jan 13, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Helen E HeslopCliona M Rooney
Dec 29, 2020·HLA : Immune Response Genetics·Manuel GuerreiroUNKNOWN Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH)
Mar 23, 2021·Frontiers in Immunology·Darel Martínez BedoyaDenis Migliorini
Mar 24, 2021·Transplantation·Jennifer LiNatasha M Rogers

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