Tracking the progeny of adoptively transferred virus-specific T cells in patients posttransplant using TCR sequencing

• Published in: Blood advances Vol. 7; no. 5; pp. 812 - 827
• Main Authors: Huisman, W., Roex, M. C. J., Hageman, L., Koster, E. A. S., Veld, S. A. J., Hoogstraten, C., van Balen, P., van Egmond, H. M., van Bergen, C. A. M., Einsele, H., Germeroth, L., Amsen, D., Falkenburg, J. H. F., Jedema, I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-03-2023; The American Society of Hematology
• Subjects: Adenoviridae Infections; Clinical Trials and Observations; Humans; Receptors, Antigen, T-Cell; Stem Cell Transplantation; T-Lymphocytes
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2022007270

•In vivo expansion of infused multiantigen-specific T-cell products in response to antigen encounter.•In vivo persistence of infused multiantigen-specific T-cell products in absence of viral reactivation.
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Adoptive cellular therapies with T cells are increasingly used to treat a variety of conditions. For instance, in a recent phase 1/2 trial, we prophylactically administered multivirus-specific T-cell products to protect recipients of T-cell–depleted allogeneic stem cell grafts against viral reactivation. To establish treatment efficacy, it is important to determine the fate of the individual transferred T-cell populations. However, it is difficult to unequivocally distinguish progeny of the transferred T-cell products from recipient- or stem cell graft–derived T cells that survived T-cell depletion during conditioning or stem cell graft manipulation. Using messenger RNA sequencing of the T-cell receptor β-chains of the individual virus-specific T-cell populations within these T-cell products, we were able to track the multiple clonal virus-specific subpopulations in peripheral blood and distinguish recipient- and stem cell graft–derived virus-specific T cells from the progeny of the infused T-cell products. We observed in vivo expansion of virus-specific T cells that were exclusively derived from the T-cell products with similar kinetics as the expansion of virus-specific T cells that could also be detected before the T-cell product infusion. In addition, we demonstrated persistence of virus-specific T cells derived from the T-cell products in most patients who did not show viral reactivation. This study demonstrates that virus-specific T cells from prophylactically infused multiantigen-specific T-cell products can expand in response to antigen encounter in vivo and even persist in the absence of early viral reactivation.