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Review
. 2019 Feb 6;8(2):200.
doi: 10.3390/jcm8020200.

Chimeric Antigen Receptor (CAR) T Cell Therapy in Acute Myeloid Leukemia (AML)

Susanne Hofmann  1 , Maria-Luisa Schubert  2 , Lei Wang  3 , Bailin He  4 , Brigitte Neuber  5 , Peter Dreger  6   7 , Carsten Müller-Tidow  8   9 , Michael Schmitt  10   11
Affiliations
Review

Chimeric Antigen Receptor (CAR) T Cell Therapy in Acute Myeloid Leukemia (AML)

Susanne Hofmann et al. J Clin Med. .

Abstract

Despite high response rates after initial chemotherapy in patients with acute myeloid leukemia (AML), relapses occur frequently, resulting in a five-year-survival by <30% of the patients. Hitherto, allogeneic hemotopoietic stem cell transplantation (allo-HSCT) is the best curative treatment option in intermediate and high risk AML. It is the proof-of-concept for T cell-based immunotherapies in AML based on the graft-versus-leukemia (GvL)-effect, but it also bears the risk of graft-versus-host disease. CD19-targeting therapies employing chimeric antigen receptor (CAR) T cells are a breakthrough in cancer therapy. A similar approach for myeloid malignancies is highly desirable. This article gives an overview on the state-of-the art of preclinical and clinical studies on suitable target antigens for CAR T cell therapy in AML patients.

Keywords: AML; CAR T cell; immunotherapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A) Chimeric antigen receptor (CAR). CARs consist of an extracellular domain generated by joining the heavy and light chain variable regions of a monoclonal antibody with a linker to form a single-chain Fv (scFv) molecule. The antigen-specific domain binds its antigen on the surface of target cells. The scFv is attached via a hinge region to the transmembrane and intracellular receptor portion. In first-generation CARs, the signaling domain is composed of the zeta- domain of a T cell receptor (TCR)/CD3 receptor complex. In second- and third-generation CARs, one or two costimulatory signaling domains are added (e.g., CD28, 4-1BB (CD137), OX-40 (CD137), or inducible T cell costimulatory (ICOS)) within their intracellular domain, respectively. (B) Innovative CAR design. Suicide gene strategies are investigated as control mechanisms for better toxicity management of CAR T cells. One example is the inducible caspase 9 (iCasp9). When the small molecule AP1903 is administered, iCasp9 domains dimerize and activate apoptosis independently of CAR activation. Dual-targeting CARs express two different antigen-specific CARs, whereas bispecific CARs bear two linked scFV within one CAR construct. To address human leukocyte antigen (HLA)-presented antigens, TCR-mimic (TCRm) CARs directing the scFv domain against a peptide-HLA complex have been developed.
Figure 2
Figure 2
Potential target antigens for CAR therapy in AML.
See this image and copyright information in PMC

References

    1. Döhner H., Weisdorf D.J., Bloomfield C.D. Acute myeloid leukemia. N. Engl. J. Med. 2015;373:1136–1152. doi: 10.1056/NEJMra1406184. - DOI - PubMed
    1. Döhner H., Estey E.H., Amadori S., Appelbaum F.R., Büchner T., Burnett A.K., Dombret H., Fenaux P., Grimwade D., Larson R.A., et al. Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the european leukemianet. Blood. 2010;115:453–474. doi: 10.1182/blood-2009-07-235358. - DOI - PubMed
    1. Eppert K., Takenaka K., Lechman E.R., Waldron L., Nilsson B., van Galen P., Metzeler K.H., Poeppl A., Ling V., Beyene J., et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat. Med. 2011;17:1086–1093. doi: 10.1038/nm.2415. - DOI - PubMed
    1. Bonnet D., Dick J.E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 1997;3:730–737. doi: 10.1038/nm0797-730. - DOI - PubMed
    1. [(accessed on 5 February 2019)]; Available online: https://seer.cancer.gov/statfacts/html/amyl.html.

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