Review
Version 1
Preserved in Portico This version is not peer-reviewed
The Black Hole: CAR T cell Therapy in AML
Version 1
: Received: 17 April 2023 / Approved: 18 April 2023 / Online: 18 April 2023 (04:22:46 CEST)
A peer-reviewed article of this Preprint also exists.
Atilla, E.; Benabdellah, K. The Black Hole: CAR T Cell Therapy in AML. Cancers 2023, 15, 2713. Atilla, E.; Benabdellah, K. The Black Hole: CAR T Cell Therapy in AML. Cancers 2023, 15, 2713.
Abstract
Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.
Keywords
Acute Myeloid Leukemia, cellular therapies, chimeric antigen T cells, T cell receptor T cells, CAR-NK cells, RNAseq
Subject
Medicine and Pharmacology, Hematology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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