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Chimeric antigen receptor T cells march into T cell malignancies

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Abstract

T cell malignancies represent a diverse collection of leukemia/lymphoma conditions in humans arising from aberrant T cells. Such malignancies are often associated with poor clinical prognoses, cancer relapse, as well as progressive resistance to anti-cancer treatments. While chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a revolutionary treatment strategy that is highly effective for treating B cell malignancies, its application as a treatment for T cell malignancies remains to be better explored. Furthermore, the effectiveness of CAR-T treatment in T cell malignancies is significantly influenced by the quality of contamination-free CAR-T cells during the manufacturing process, as well as by multiple characteristics of such malignancies, including the sharing of antigens across normal and malignant T cells, fratricide, and T cell aplasia. In this review, we provide a detailed account of the current developments in the clinical application of CAR-T therapy to treat T cell malignancies, offer strategies for addressing current challenges, and outline a roadmap toward its effective implementation as a broad treatment option for this condition.

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Abbreviations

CAR-T:

Chimeric antigen receptor T

T-ALL/LBL:

T cell acute lymphoblastic leukemia/lymphoma

NHL:

Non-Hodgkin's lymphoma

PTCLs:

Peripheral T cell lymphomas

R/R:

Relapsed/recurrence

allo-HSCT:

Allogeneic hematopoietic stem cell transplantation

ICIs:

Immune checkpoint inhibitors

FDA:

Food and Drug Administration

TCR:

T cell receptor

DN:

Double-negative

DP:

Double-positive

DNT:

Double-negative T

NKT:

Natural killer T

Tregs:

Regulatory T cells

MHC:

Major histocompatibility complex

TAAs:

Tumor-associated antigens

scFv:

Single-chain variable fragments

APCs:

Antigen-presenting cells

CTCLs:

Cutaneous T cell lymphomas

CBE:

Cytosine base editor

ZFN:

Zinc finger nuclease

TALEN:

Transcription activator-like effector nuclease

DSB:

Double-strand breaks

GVHD:

Graft-versus-host disease

PEBL:

Protein expression blocker

ICANS:

Immune effector cell-associated neurotoxicity syndrome

Dox:

Doxycycline

NK:

Natural killer

mRNA:

Messenger RNA

AAV:

Adeno-associated virus

qPCR:

Quantitative PCR

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Acknowledgements

Manuscript editor Julian Heng (Remotely Consulting, Australia) provided professional English language editing of this article. Dr. Sun Bin provided the funding support.

Funding

This work was financially supported by the National Natural Science Foundation of China (No. 82103107).

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  1. Department of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Jie Tang & Xudong Zhao

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  1. Jie Tang
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  2. Xudong Zhao
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TJ drafted the original manuscript and visualized the tables and figures. XZ designed the review and critically revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xudong Zhao.

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Tang, J., Zhao, X. Chimeric antigen receptor T cells march into T cell malignancies. J Cancer Res Clin Oncol 149, 13459–13475 (2023). https://doi.org/10.1007/s00432-023-05148-5

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