Advancing CART therapy for acute myeloid leukemia: recent breakthroughs and strategies for future development

Lorena Pérez-Amill; Àlex Bataller; Julio Delgado; Jordi Esteve; Manel Juan; Nela Klein-González

doi:10.3389/fimmu.2023.1260470

Advancing CART therapy for acute myeloid leukemia: recent breakthroughs and strategies for future development

Front Immunol. 2023 Nov 30:14:1260470. doi: 10.3389/fimmu.2023.1260470. eCollection 2023.

Authors

Lorena Pérez-Amill^{1

2

3}, Àlex Bataller^{4

5}, Julio Delgado^{1

4

6}, Jordi Esteve^{1

4

6}, Manel Juan^{1

6

3

7}, Nela Klein-González^{1

2

3}

Affiliations

¹ Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
² Gyala Therapeutics S.L, Barcelona, Spain.
³ Department of Immunology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Barcelona, Spain.
⁴ Department of Haematology, Institut Clínic de Malalties Hematològiques i Oncològiques (ICHMO), Hospital Clínic de Barcelona, Barcelona, Spain.
⁵ Josep Carreras Leukemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain.
⁶ Universitat de Barcelona, Barcelona, Spain.
⁷ Hospital Sant Joan de Déu, Universidad de Barcelona, Barcelona, Spain.

Abstract

Chimeric antigen receptor (CAR) T therapies are being developed for acute myeloid leukemia (AML) on the basis of the results obtained for other haematological malignancies and the need of new treatments for relapsed and refractory AML. The biggest challenge of CART therapy for AML is to identify a specific target antigen, since antigens expressed in AML cells are usually shared with healthy haematopoietic stem cells (HSC). The concomitant expression of the target antigen on both tumour and HSC may lead to on-target/off-tumour toxicity. In this review, we guide researchers to design, develop, and translate to the clinic CART therapies for the treatment of AML. Specifically, we describe what issues have to be considered to design these therapies; what in vitro and in vivo assays can be used to prove their efficacy and safety; and what expertise and facilities are needed to treat and manage patients at the hospital.

Keywords: acute myeloid leukemia; chimeric antigen receptor; cytopenia; hematologic toxicity; myelotoxicity; on-target/off-tumor toxicity.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Hematopoietic Stem Cells / pathology
Humans
Immunotherapy, Adoptive / adverse effects
Immunotherapy, Adoptive / methods
Leukemia, Myeloid, Acute*
T-Lymphocytes*

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Supported by Secretaria d’Universitat i Recerca del Departament d’Empresa i Coneixement, Generalitat de Catalunya, project 2020PANDE00079. LP-A is funded by “Programa Torres Quevedo” grant PTQ2020-011012 funded by MCIN/AEI/10.13039/501100011033; Gyala Therapeutics and FCRB-IDIBAPS are funded by project CPP2021-008553 funded by MCIN/AEI/10. 13039/501100011033 and by the European Union ‘NextGenerationEU/PRTR; Gyala Therapeutics is funded by a project from CDTI with the collaboration of the Ministry of Science and Innovation and co-financed by the European Union Next Generation EU with the file number SNEO-2021111060 (subsidized by CDTI). The project that gave rise to these results has received funding from ”la Caixa” Foundation*under the grant agreement LCF/PR/SP23/52950004.