Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells

Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells

Despite the considerable progress in acute myeloid leukemia (AML) treatment, relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is still frequent and associated with a poor prognosis. Relapse has been shown to be correlated with an incomplete eradication of CD34+ leukemic stem c...

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Main Authors: Faisal Al Agrafi, Ahmed Gaballa, Paula Hahn, Lucas C. M. Arruda, Adrian C. Jaramillo, Maartje Witsen, Sören Lehmann, Björn Önfelt, Michael Uhlin, Arwen Stikvoort
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:OncoImmunology
Subjects:
Acute myeloid leukemia
bispecific antibodies
cancer immunology
CD34
γδ T-cells
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2024.2379063
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Summary:Despite the considerable progress in acute myeloid leukemia (AML) treatment, relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is still frequent and associated with a poor prognosis. Relapse has been shown to be correlated with an incomplete eradication of CD34+ leukemic stem cells prior to HSCT. Previously, we have shown that a novel CD34-directed, bispecific T-cell engager (BTE) can efficiently redirect the T-cell effector function toward cancer cells, thus eliminating leukemic cells in vitro and in vivo. However, its impact on γδ T-cells is still unclear. In this study, we tested the efficacy of the CD34-specific BTE using in vitro expanded γδ T-cells as effectors. We showed that the BTEs bind to γδ T-cells and CD34+ leukemic cell lines and induce target cell killing in a dose-dependent manner. Additionally, γδ T-cell mediated killing was found to be superior to αβ T-cell mediated cytotoxicity. Furthermore, we observed that only in the presence of BTE the γδ T-cells induced primary AML blast killing in vitro. Importantly, our results show that γδ T-cells did not target the healthy CD34intermediate endothelial blood–brain barrier cell line (hCMEC/D3) nor lysed CD34+ HSCs from healthy bone marrow samples.
ISSN:2162-402X

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