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实体瘤下一代免疫治疗中的 CAR 工程革命。

Revolution of CAR Engineering For Next-Generation Immunotherapy In Solid Tumors.

机构信息

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Suzhou Cancer Center Core Laboratory, Suzhou Municipal Hospital, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.

出版信息

Front Immunol. 2022 Jul 12;13:936496. doi: 10.3389/fimmu.2022.936496. eCollection 2022.


DOI:10.3389/fimmu.2022.936496
PMID:35903099
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9315443/
Abstract

Chimeric antigen receptor (CAR)-T cells have enormous potentials for clinical therapies. The CAR-T therapy has been approved for treating hematological malignancies. However, their application is limited in solid tumors owing to antigen loss and mutation, physical barriers, and an immunosuppressive tumor microenvironment. To overcome the challenges of CAR-T, increasing efforts are put into developing CAR-T to expand its applied ranges. Varied receptors are utilized for recognizing tumor-associated antigens and relieving immunosuppression. Emerging co-stimulatory signaling is employed for CAR-T activation. Furthermore, other immune cells such as NK cells and macrophages have manifested potential for delivering CAR. Hence, we collected and summarized the last advancements of CAR engineering from three aspects, namely, the ectodomains, endogenous domains, and immune cells, aiming to inspire the design of next-generation adoptive immunotherapy for treating solid tumors.

摘要

嵌合抗原受体 (CAR)-T 细胞在临床治疗方面具有巨大的潜力。CAR-T 疗法已被批准用于治疗血液系统恶性肿瘤。然而,由于抗原丢失和突变、物理屏障以及免疫抑制性肿瘤微环境,其在实体瘤中的应用受到限制。为了克服 CAR-T 的挑战,人们正在努力开发 CAR-T,以扩大其应用范围。不同的受体被用于识别肿瘤相关抗原和解除免疫抑制。新兴的共刺激信号被用于 CAR-T 的激活。此外,NK 细胞和巨噬细胞等其他免疫细胞也表现出递送 CAR 的潜力。因此,我们从胞外结构域、内源性结构域和免疫细胞三个方面收集和总结了 CAR 工程的最新进展,旨在为设计用于治疗实体瘤的下一代过继免疫疗法提供灵感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/e6a9819c6e91/fimmu-13-936496-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/07f06c2736b7/fimmu-13-936496-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/2c339541a2b5/fimmu-13-936496-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/a52132958df2/fimmu-13-936496-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/0bad7ae845a2/fimmu-13-936496-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/8f6137b0e27e/fimmu-13-936496-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/e6a9819c6e91/fimmu-13-936496-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/07f06c2736b7/fimmu-13-936496-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/2c339541a2b5/fimmu-13-936496-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/a52132958df2/fimmu-13-936496-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/0bad7ae845a2/fimmu-13-936496-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/8f6137b0e27e/fimmu-13-936496-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f7/9315443/e6a9819c6e91/fimmu-13-936496-g006.jpg

相似文献

[1]
Revolution of CAR Engineering For Next-Generation Immunotherapy In Solid Tumors.

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[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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[10]
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引用本文的文献

[1]
Overcoming barriers in glioblastoma: The potential of CAR T cell immunotherapy.

Theranostics. 2025-6-12

[2]
Unleashing the power of CAR-M therapy in solid tumors: a comprehensive review.

Front Immunol. 2025-6-12

[3]
Harnessing delta-like ligand 3: bridging biomarker discovery to next-generation immunotherapies in refractory small cell lung cancer.

Front Immunol. 2025-5-27

[4]
Efficacy and safety of novel multiple-chain DAP-CAR-T cells targeting mesothelin in ovarian cancer and mesothelioma: a single-arm, open-label and first-in-human study.

Genome Med. 2024-11-15

[5]
Optogenetically engineered Septin-7 enhances immune cell infiltration of tumor spheroids.

Proc Natl Acad Sci U S A. 2024-10-29

[6]
A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?

Front Immunol. 2024

[7]
CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn.

Nat Rev Clin Oncol. 2024-1

[8]
CAR-NKT cell therapy: a new promising paradigm of cancer immunotherapy.

Cancer Cell Int. 2023-5-8

[9]
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors.

Biomolecules. 2023-3-2

[10]
Nanoparticle-Based Drug Delivery Systems Targeting Tumor Microenvironment for Cancer Immunotherapy Resistance: Current Advances and Applications.

Pharmaceutics. 2022-9-21

本文引用的文献

[1]
Isolation of Neoantigen-Specific Human T Cell Receptors from Different Human and Murine Repertoires.

Cancers (Basel). 2022-4-6

[2]
Natural killer cell therapy: A new frontier for obesity-associated cancer.

Cancer Lett. 2022-6-1

[3]
Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies.

Arch Immunol Ther Exp (Warsz). 2021-12-12

[4]
Novel two-chain structure utilizing KIRS2/DAP12 domain improves the safety and efficacy of CAR-T cells in adults with r/r B-ALL.

Mol Ther Oncolytics. 2021-8-28

[5]
IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin.

J Hematol Oncol. 2021-7-29

[6]
Co-stimulatory agonists: An insight into the immunotherapy of cancer.

EXCLI J. 2021-6-9

[7]
A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains.

Nat Rev Clin Oncol. 2021-11

[8]
Engineered Cytokine Signaling to Improve CAR T Cell Effector Function.

Front Immunol. 2021

[9]
Distinct functions of CAR-T cells possessing a dectin-1 intracellular signaling domain.

Gene Ther. 2023-5

[10]
Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors.

Sci Transl Med. 2021-3-24

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