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Acute Leukemias

Anti-leukemia effect of ex vivo expanded DNT cells from AML patients: a potential novel autologous T-cell adoptive immunotherapy

Leukemia volume 25, pages 1415–1422 (2011)Cite this article

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Abstract

CD3+CD56−, CD4 and CD8 double negative T (DNT) cells comprise 1–3% of peripheral blood (PB) mononuclear cells. Their role in tumor immunity remains largely unknown due to their limited numbers and lack of effective methods to expand them. Here we developed a novel protocol by which DNT cells can be expanded ex vivo to therapeutic levels in 2 weeks from 13 of 16 acute myeloid leukemia (AML) patients during chemotherapy-induced complete remission. The expanded DNT cells expressed similar or higher levels of interferon-γ and tumor necrosis factor-α and Granzyme B as that seen in bulk activated CD8T cells from the same patient but significantly higher levels of perforin. The expanded DNT cells could effectively kill both allogeneic and autologous primary CD34+ leukemic blasts isolated from PB of AML patients in a perforin-dependant manner. These results demonstrate, for the first time, that DNT cells from AML patients can be expanded ex vivo even after intensive chemotherapy, and are effective at killing both allogeneic and autologous primary leukemic blasts. These findings warrant studies further exploring the potential of DNT cells as a novel adjuvant immunotherapy to decrease the risk of relapse in patients with AML and, perhaps, other cancers.

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Acknowledgements

This study was funded by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario and the Canadian Cancer Society (grant 020516) to LZ. LZ is a Maria H Bacardi Chair in Transplantation. We would like to thank Dr Andre Schuh for his insightful comments.

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Author notes

  1. S Merims, X Li and B Joe: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Laboratory Medicine and Pathobiology, and Immunology, Toronto General Research Institute, Toronto, Ontario, Canada

    S Merims, X Li, B Joe, P Dokouhaki, M Han & L Zhang

  2. Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    R W Childs

  3. Shanghai Institute of Hematology, Rui-jin Hospital, Shanghai, China

    Z-Y Wang

  4. Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Ontario, Canada

    V Gupta & M D Minden

  5. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    L Zhang

  6. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    L Zhang

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Merims, S., Li, X., Joe, B. et al. Anti-leukemia effect of ex vivo expanded DNT cells from AML patients: a potential novel autologous T-cell adoptive immunotherapy. Leukemia 25, 1415–1422 (2011). https://doi.org/10.1038/leu.2011.99

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