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Developing Strategies to Improve the Efficacy of CAR-T Therapy for Acute Myeloid Leukemia

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Opinion statement

Acute myeloid leukemia (AML) is a fatal blood malignancy. With the development of immunotherapy, particularly chimeric antigen receptor T cells (CAR-T), the treatment of AML has undergone a significant change. Despite its advantages, CAR-T still faces a number of limitations and challenges while treating AML. Finding novel targets, altering the structure of CAR to increase efficacy while lowering side effects, and using double-target CAR and logic circuits are typical examples of key to answer these problems. With the advancement of gene editing technology, gene editing of tumor cells or normal cells to create therapeutic effects has grown in popularity. Additionally, the combination of multiple drugs is routinely used to address some of the obstacles and difficulties associated with CAR-T therapy. The review’s primary goal was to summarize recent strategies and developments of CAR-T therapy for AML.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

ASC:

Allogeneic stem cell

AZA:

Azacitidine

BM:

Bone morrow

BCMA:

B cell maturation antigen

CAR:

Chimeric antigen receptor

CCR:

Chimeric costimulatory receptor

CIK:

Cytokine-induced killer

CR:

Complete remission

CRS:

Cytokine release syndrome

CRTSPR-Cas9:

Clustered regularly interspaces short palindromic repeats and CRISPR associated protein 9

DAC:

Decitabine

DL:

Dose level

DLT:

Dose-limiting toxicities

DLBCL:

Diffuse large B cell lymphoma

GVHD:

Graft versus host disease

FAO:

Fatty acid oxidation

FRβ:

Folate receptor β

HDACi:

Histone deacetylase inhibitor

HER-2:

Human epidermal growth factor receptor 2

HIF-1α:

Hypoxia inducible factor-1α

IL:

Interleukin

LeY:

Lewis Y

LILRB4:

Leukocyte immunoglobulin-like receptor B4

MM:

Multiple myeloma

NKG2D:

Natural killer group 2 D

NR4A:

Nuclear receptor subfamily 4 group A

OTOT:

On-target, off-tumor toxicity

PD-1:

Programmed cell death protein-1

R/R(r/r):

Relapsed and/or refractory

Siglec-6:

Sialic acid-binding immunoglobulin-like lectin 6

TCR:

T cell receptor

TME:

Tumor microenvironment

TRAC:

T cell receptor alpha constant gene

VPA:

Valproic acid

WT1:

Wilms tumor 1

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Acknowledgements

We thank all authors contributing to this work.

Funding

This work was supported by grants from the General Project of the National Natural Science Foundation of China (81970180), the Science and Technology Project of Tianjin Municipal Health Committee (TJWJ2022QN030), the Key Projects of Tianjin Applied Basic Research and Multi-Investment Fund (21JCZDJC01240), the Science and Technology Project of Tianjin Municipal Health Committee (TJWJ2022XK018), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-056B), Tianjin Municipal Natural Science Foundation (22JCQNJC00820), Tianjin Health Research Project (TJWJ2023QN027), Tianjin Health Bureau Project (ZC20074), and Tianjin Key Medical Discipline (Specialty) Construction Project (TJWJ2023XK010).

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  1. Ruiting Guo and Jile Liu have contributed equally to this work.

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  1. First Center, Clinic College of Tianjin Medical University, Tianjin, 300192, China

    Shujing Guo MMed, Mahara Sadhana MMed, Ruiting Guo MMed & Jile Liu MMed

  2. Emergency Department, Tianjin First Central Hospital, Tianjin, 300192, China

    Xuejin Gao MD

  3. Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, China

    Wenyi Lu MD & Ming Feng Zhao MD

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SG drafted the manuscript; SG and XG drew the figure and reviewed the literature. MZ, LW, JL, and RG provided critical revision of the paper. All authors participated in the process of drafting and revising the manuscript. All authors have read and approved the final manuscript.

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Guo, S., Gao, X., Sadhana, M. et al. Developing Strategies to Improve the Efficacy of CAR-T Therapy for Acute Myeloid Leukemia. Curr. Treat. Options in Oncol. 24, 1614–1632 (2023). https://doi.org/10.1007/s11864-023-01140-w

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