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Is Hematopoietic Stem Cell Transplantation Required to Unleash the Full Potential of Immunotherapy in Acute Myeloid Leukemia?

1
Dendritic Cell Research, ANZAC Research Institute, Concord 2139, NSW, Australia
2
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown 2050, NSW, Australia
3
The University of Sydney, Camperdown 2039, NSW, Australia
4
Department of Haematology, Concord Repatriation and General Hospital, Concord 2039, NSW, Australia
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(2), 554; https://doi.org/10.3390/jcm9020554
Received: 31 January 2020 / Revised: 13 February 2020 / Accepted: 13 February 2020 / Published: 18 February 2020
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
From monoclonal antibodies (mAbs) to Chimeric Antigen Receptor (CAR) T cells, immunotherapies have enhanced the efficacy of treatments against B cell malignancies. The same has not been true for Acute Myeloid Leukemia (AML). Hematologic toxicity has limited the potential of modern immunotherapies for AML at preclinical and clinical levels. Gemtuzumab Ozogamicin has demonstrated hematologic toxicity, but the challenge of preserving normal hematopoiesis has become more apparent with the development of increasingly potent immunotherapies. To date, no single surface molecule has been identified that is able to differentiate AML from Hematopoietic Stem and Progenitor Cells (HSPC). Attempts have been made to spare hematopoiesis by targeting molecules expressed only on later myeloid progenitors as well as AML or using toxins that selectively kill AML over HSPC. Other strategies include targeting aberrantly expressed lymphoid molecules or only targeting monocyte-associated proteins in AML with monocytic differentiation. Recently, some groups have accepted that stem cell transplantation is required to access potent AML immunotherapy and envision it as a rescue to avoid severe hematologic toxicity. Whether it will ever be possible to differentiate AML from HSPC using surface molecules is unclear. Unless true specific AML surface targets are discovered, stem cell transplantation could be required to harness the true potential of immunotherapy in AML. View Full-Text
Keywords: AML immunotherapy; hematopoietic stem cell toxicity; Chimeric Antigen Receptor (CAR) T cells; antibody drug conjugates AML immunotherapy; hematopoietic stem cell toxicity; Chimeric Antigen Receptor (CAR) T cells; antibody drug conjugates
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MDPI and ACS Style

Abadir, E.; Gasiorowski, R.E.; Silveira, P.A.; Larsen, S.; Clark, G.J. Is Hematopoietic Stem Cell Transplantation Required to Unleash the Full Potential of Immunotherapy in Acute Myeloid Leukemia? J. Clin. Med. 2020, 9, 554.

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