Is hematopoietic stem cell transplantation required to unleash the full potential of immunotherapy in acute myeloid leukemia?

Edward Abadir, Robin E. Gasiorowski, Pablo A. Silveira, Stephen Larsen, Georgina J. Clark

Research output: Contribution to journalReview article

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Abstract

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.

Original languageEnglish
Article number554
Pages (from-to)1-15
Number of pages15
JournalJournal of Clinical Medicine
Volume9
Issue number2
DOIs
Publication statusPublished - 18 Feb 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • AML immunotherapy
  • hematopoietic stem cell toxicity
  • Chimeric Antigen Receptor (CAR) T cells
  • antibody drug conjugates

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