Generation and infusion of multi-antigen-specific T cells to prevent complications early after T-cell depleted allogeneic stem cell transplantation—a phase I/II study

Roex MCJ, Van Balen P, Germeroth L, Hageman L, Van Egmond E, Veld SAJ, Hoogstraten C, Van Liempt E, Zwaginga JJ, De Wreede LC, Meij P, Vossen ACTM, Danhof S, Einsele H, Schaafsma MR, Veelken H, Halkes CJM, Jedema I, Falkenburg JHF (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Leukemia Springer Nature

Book Volume: 34

Pages Range: 831-844

Journal Issue: 3

DOI: 10.1038/s41375-019-0600-z

Abstract

Prophylactic infusion of selected donor T cells can be an effective method to restore specific immunity after T-cell-depleted allogeneic stem cell transplantation (TCD-alloSCT). In this phase I/II study, we aimed to reduce the risk of viral complications and disease relapses by administrating donor-derived CD8^pos T cells directed against cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus antigens, tumor-associated antigens (TAA) and minor histocompatibility antigens (MiHA). Twenty-seven of thirty-six screened HLA-A*02:01^pos patients and their CMV^pos and/or EBV^pos donors were included. Using MHC-I-Streptamers, 27 T-cell products were generated containing a median of 5.2 × 10⁶ cells. Twenty-four products were administered without infusion-related complications at a median of 58 days post alloSCT. No patients developed graft-versus-host disease during follow-up. Five patients showed disease progression without coinciding expansion of TAA/MiHA-specific T cells. Eight patients experienced CMV- and/or EBV-reactivations. Four of these reactivations were clinically relevant requiring antiviral treatment, of which two progressed to viral disease. All resolved ultimately. In 2/4 patients with EBV-reactivations and 6/8 patients with CMV-reactivations, viral loads were followed by the expansion of donor-derived virus target-antigen-specific T cells. In conclusion, generation of multi-antigen-specific T-cell products was feasible, infusions were well tolerated and expansion of target-antigen-specific T cells coinciding viral reactivations was illustrated in the majority of patients.

Involved external institutions

Leiden University

Netherlands (NL) Juno Therapeutics

Germany (DE) Universitätsklinikum Würzburg

Germany (DE) Medisch Spectrum Twente (MST)

Netherlands (NL)

How to cite

APA:

Roex, M.C.J., Van Balen, P., Germeroth, L., Hageman, L., Van Egmond, E., Veld, S.A.J.,... Falkenburg, J.H.F. (2020). Generation and infusion of multi-antigen-specific T cells to prevent complications early after T-cell depleted allogeneic stem cell transplantation—a phase I/II study. Leukemia, 34(3), 831-844. https://doi.org/10.1038/s41375-019-0600-z

MLA:

Roex, Marthe C. J., et al. "Generation and infusion of multi-antigen-specific T cells to prevent complications early after T-cell depleted allogeneic stem cell transplantation—a phase I/II study." Leukemia 34.3 (2020): 831-844.

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