Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL
Duell J, Dittrich M, Bedke T, Mueller T, Eisele F, Rosenwald A, Rasche L, Hartmann E, Dandekar T, Einsele H, Topp MS (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 31
Pages Range: 2181-2190
Journal Issue: 10
DOI: 10.1038/leu.2017.41
Abstract
Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab. Blinatumomab responders (n=22) had an average of 4.82% Tregs (confidence interval (CI): 1.79-8.34%) in the peripheral blood, whereas non-responders (n=20) demonstrated 10.25% Tregs (CI: 3.36-65.9%). All other tested markers showed either no prediction value or an inferior prediction level including blast BM counts and the classical enzyme marker lactate dehydrogenase. With a cutoff of 8.525%, Treg enumeration can identify 100% of all blinatumomab responders and exclude 70% of the non-responders. The effect is facilitated by blinatumomab-activated Tregs, leading to interleukin-10 production, resulting in suppression of T-cell proliferation and reduced CD8-mediated lysis of ALL cells. Proliferation of patients' T cells can be restored by upfront removal of Tregs. Thus, enumeration of Treg identifies r/r ALL patients with a high response rate to blinatumomab. Therapeutic removal of Tregs may convert blinatumomab non-responders to responders.
Involved external institutions
Universitätsklinikum Würzburg
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
How to cite
APA:
Duell, J., Dittrich, M., Bedke, T., Mueller, T., Eisele, F., Rosenwald, A.,... Topp, M.S. (2017). Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL. Leukemia, 31(10), 2181-2190. https://doi.org/10.1038/leu.2017.41
MLA:
Duell, J., et al. "Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL." Leukemia 31.10 (2017): 2181-2190.
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