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用于癌症治疗的多抗原靶向嵌合抗原受体 T 细胞。

Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy.

机构信息

Molecular and Immunological Department, Bio-therapeutic Department Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.

出版信息

J Hematol Oncol. 2019 Nov 29;12(1):128. doi: 10.1186/s13045-019-0813-7.

DOI:10.1186/s13045-019-0813-7
PMID:31783889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6884912/
Abstract

The approval of two chimeric antigen receptor-modified T cell types by the US Food and Drug Administration (FDA) for the treatment of hematologic malignancies is a milestone in immunotherapy; however, the application of CAR-T cells has been limited by antigen escape and on-target, off-tumor toxicities. Therefore, it may be a potentially effective strategy to select appropriate targets and to combine multi-antigen-targeted CAR-T cells with "OR", "AND" and "NOT" Boolean logic gates. We summarize the current limitations of CAR-T cells as well as the efficacy and safety of logic-gated CAR-T cells in antitumor therapy. This review will help to explore more optimized strategies to expand the CAR-T cell therapeutic window.

摘要

美国食品和药物管理局（FDA）批准两种嵌合抗原受体修饰的 T 细胞用于治疗血液系统恶性肿瘤，这是免疫治疗的一个里程碑；然而，CAR-T 细胞的应用受到抗原逃逸和靶内、脱靶毒性的限制。因此，选择合适的靶点，并结合多抗原靶向 CAR-T 细胞与“或”、“与”和“非”布尔逻辑门，可能是一种潜在有效的策略。我们总结了 CAR-T 细胞目前的局限性，以及逻辑门控 CAR-T 细胞在抗肿瘤治疗中的疗效和安全性。这篇综述将有助于探索更优化的策略来扩大 CAR-T 细胞的治疗窗口。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb0/6884912/46684f04a54b/13045_2019_813_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb0/6884912/e1f6a4fddbfe/13045_2019_813_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb0/6884912/46684f04a54b/13045_2019_813_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb0/6884912/e1f6a4fddbfe/13045_2019_813_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb0/6884912/46684f04a54b/13045_2019_813_Fig2_HTML.jpg

相似文献

[1]
Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy.

J Hematol Oncol. 2019-11-29

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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Mamm Genome. 2018-7-9

[10]
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Clin Pharmacol Ther. 2019-1

引用本文的文献

[1]
Dual targeting of BCMA and SLAMF7 with the CARtein system: chimeric antigen receptors with intein-mediated splicing elicit specific T cell activation against multiple myeloma.

Front Immunol. 2025-7-31

[2]
Computational structural optimization enhances IL13Rα2 - B7-H3 tandem CAR T cells to overcome antigen-heterogeneity-mediated tumor escape.

Mol Ther. 2025-8-8

[3]
Chronic Lymphocytic Leukemia: Novel Therapeutic Targets Under Investigation.

Cancers (Basel). 2025-7-10

[4]
CAR-iNKT cells: redefining the frontiers of cellular immunotherapy.

Front Immunol. 2025-7-11

[5]
CAR T-cell therapy in hematologic and solid malignancies: mechanisms, clinical applications, and future directions.

Med Oncol. 2025-7-25

[6]
Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.

Curr Issues Mol Biol. 2025-4-10

[7]
Targets for CAR Therapy in Multiple Myeloma.

Int J Mol Sci. 2025-6-24

[8]
Nanobody-Based CAR NK Cells for Possible Immunotherapy of Mesothelin Tumors.

Immune Netw. 2025-6-13

[9]
Barriers and solutions for CAR-T therapy in solid tumors.

Cancer Gene Ther. 2025-6-27

[10]
iPSC-derived trimodal T cells engineered with CAR, TCR, and hnCD16 modalities can overcome antigen escape in heterogeneous tumors.

Cell Rep Med. 2025-7-15

本文引用的文献

[1]
Target selection for CAR-T therapy.

J Hematol Oncol. 2019-6-20

[2]
Haploidentical CD19/CD22 bispecific CAR-T cells induced MRD-negative remission in a patient with relapsed and refractory adult B-ALL after haploidentical hematopoietic stem cell transplantation.

J Hematol Oncol. 2019-6-10

[3]
CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape.

Nature. 2019-3-27

[4]
Expanding the Therapeutic Window for CAR T Cell Therapy in Solid Tumors: The Knowns and Unknowns of CAR T Cell Biology.

Front Immunol. 2018-10-26

[5]
Enhancing the Potency and Specificity of Engineered T Cells for Cancer Treatment.

Cancer Discov. 2018-6-7

[6]
CAR T cell immunotherapy for human cancer.

Science. 2018-3-23

[7]
Nanobody Based Dual Specific CARs.

Int J Mol Sci. 2018-1-30

[8]
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.

N Engl J Med. 2018-2-1

[9]
CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.

Nat Med. 2017-11-20

[10]
FDA Approves Second CAR T-cell Therapy.

Cancer Discov. 2018-1

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