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Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML

1
Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria
2
Ludwig Boltzmann Institute for Hematology & Oncology, Medical University of Vienna, 1090 Vienna, Austria
3
Department of Radiotherapy, Medical University of Vienna, 1090 Vienna, Austria
4
Division of Blood and Bone Marrow Transplantation, Department of Internal Medicine I, Medical University of Vienna, 1090 Vienna, Austria
5
Department of Internal Medicine V (Hematology & Oncology), Medical University of Innsbruck, 1090 Innsbruck, Austria
6
Medical Clinic 3, Oncology, Hematology, Immunoncology & Rheumatology, University Clinic Bonn (UKB), 53127 Bonn, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(17), 4233; https://doi.org/10.3390/ijms20174233
Received: 17 July 2019 / Revised: 25 August 2019 / Accepted: 27 August 2019 / Published: 29 August 2019
(This article belongs to the Special Issue Advances in Molecular Biology and Targeted Therapy of Leukemias 2.0)
The concept of leukemic stem cells (LSC) has been developed with the idea to explain the clonal hierarchies and architectures in leukemia, and the more or less curative anti-neoplastic effects of various targeted drugs. It is now widely accepted that curative therapies must have the potential to eliminate or completely suppress LSC, as only these cells can restore and propagate the malignancy for unlimited time periods. Since LSC represent a minor cell fraction in the leukemic clone, little is known about their properties and target expression profiles. Over the past few years, several cell-specific immunotherapy concepts have been developed, including new generations of cell-targeting antibodies, antibody–toxin conjugates, bispecific antibodies, and CAR-T cell-based strategies. Whereas such concepts have been translated and may improve outcomes of therapy in certain lymphoid neoplasms and a few other malignancies, only little is known about immunological targets that are clinically relevant and can be employed to establish such therapies in myeloid neoplasms. In the current article, we provide an overview of the immunologically relevant molecular targets expressed on LSC in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In addition, we discuss the current status of antibody-based therapies in these malignancies, their mode of action, and successful examples from the field. View Full-Text
Keywords: AML; CML; leukemic stem cells; CAR-T cell therapy; bispecific antibodies; precision medicine AML; CML; leukemic stem cells; CAR-T cell therapy; bispecific antibodies; precision medicine
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MDPI and ACS Style

Valent, P.; Sadovnik, I.; Eisenwort, G.; Bauer, K.; Herrmann, H.; Gleixner, K.V.; Schulenburg, A.; Rabitsch, W.; Sperr, W.R.; Wolf, D. Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML. Int. J. Mol. Sci. 2019, 20, 4233. https://doi.org/10.3390/ijms20174233

AMA Style

Valent P, Sadovnik I, Eisenwort G, Bauer K, Herrmann H, Gleixner KV, Schulenburg A, Rabitsch W, Sperr WR, Wolf D. Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML. International Journal of Molecular Sciences. 2019; 20(17):4233. https://doi.org/10.3390/ijms20174233

Chicago/Turabian Style

Valent, Peter, Irina Sadovnik, Gregor Eisenwort, Karin Bauer, Harald Herrmann, Karoline V. Gleixner, Axel Schulenburg, Werner Rabitsch, Wolfgang R. Sperr, and Dominik Wolf. 2019. "Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML" International Journal of Molecular Sciences 20, no. 17: 4233. https://doi.org/10.3390/ijms20174233

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