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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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2379063 |
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| author | Faisal Al Agrafi Ahmed Gaballa Paula Hahn Lucas C. M. Arruda Adrian C. Jaramillo Maartje Witsen Sören Lehmann Björn Önfelt Michael Uhlin Arwen Stikvoort |
| author_facet | Faisal Al Agrafi Ahmed Gaballa Paula Hahn Lucas C. M. Arruda Adrian C. Jaramillo Maartje Witsen Sören Lehmann Björn Önfelt Michael Uhlin Arwen Stikvoort |
| author_sort | Faisal Al Agrafi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ca872293916e48378654b84df2a21822 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-ca872293916e48378654b84df2a218222024-12-03T13:49:34ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2379063Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cellsFaisal Al Agrafi0Ahmed Gaballa1Paula Hahn2Lucas C. M. Arruda3Adrian C. Jaramillo4Maartje Witsen5Sören Lehmann6Björn Önfelt7Michael Uhlin8Arwen Stikvoort9Healthy Aging Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Kingdom of Saudi ArabiaDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDepartment of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, SwedenDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDepartment of Medicine Huddinge, Karolinska Institutet, Center for Hematology and Regenerative Medicine, Stockholm, SwedenDespite 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.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2379063Acute myeloid leukemiabispecific antibodiescancer immunologyCD34γδ T-cells |
| spellingShingle | Faisal Al Agrafi Ahmed Gaballa Paula Hahn Lucas C. M. Arruda Adrian C. Jaramillo Maartje Witsen Sören Lehmann Björn Önfelt Michael Uhlin Arwen Stikvoort Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells OncoImmunology Acute myeloid leukemia bispecific antibodies cancer immunology CD34 γδ T-cells |
| title | Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells |
| title_full | Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells |
| title_fullStr | Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells |
| title_full_unstemmed | Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells |
| title_short | Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells |
| title_sort | selective lysis of acute myeloid leukemia cells by cd34 cd3 bispecific antibody through the activation of γδ t cells |
| topic | Acute myeloid leukemia bispecific antibodies cancer immunology CD34 γδ T-cells |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2379063 |
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