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CAR-T 细胞免疫疗法治疗实体瘤的综合临床评估:前进之路还是死胡同?

Comprehensive clinical evaluation of CAR-T cell immunotherapy for solid tumors: a path moving forward or a dead end?

机构信息

Oncology Unit, Sotiria General Hospital, National and Kapodistrian University of Athens, 152 Mesogeion Avenue, 11527, Athens, Greece.

Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Attica, Greece.

出版信息

J Cancer Res Clin Oncol. 2023 Jun;149(6):2709-2734. doi: 10.1007/s00432-022-04547-4. Epub 2022 Dec 24.


DOI:10.1007/s00432-022-04547-4
PMID:36564524
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10129996/
Abstract

INTRODUCTION: Chimeric Antigen Receptor (CAR)-T cell therapy is a form of adoptive cell therapy that has demonstrated tremendous results in the treatment of hematopoietic malignancies, leading to the US Food and Drug Administration (FDA) approval of four CD19-targeted CAR-T cell products. With the unprecedented success of CAR-T cell therapy in hematological malignancies, hundreds of preclinical studies and clinical trials are currently undergoing to explore the translation of this treatment to solid tumors. However, the clinical experience in non-hematologic malignancies has been less encouraging, with only a few patients achieving complete responses. Tumor-associated antigen heterogeneity, inefficient CAR-T cell trafficking and the immunosuppressive tumor microenvironment are considered as the most pivotal roadblocks in solid tumor CAR-T cell therapy. MATERIALS AND METHODS: We reviewed the relevant literature/clinical trials for CAR-T cell immunotherapy for solid tumors from Pubmed and ClinicalTrials.gov. CONCLUSION: Herein, we provide an update on solid tumor CAR-T cell clinical trials, focusing on the studies with published results. We further discuss some of the key hurdles that CAR-T cell therapy is encountering for solid tumor treatment as well as the strategies that are exploited to overcome these obstacles.

摘要

简介:嵌合抗原受体 (CAR)-T 细胞疗法是一种过继细胞疗法,在治疗血液恶性肿瘤方面取得了巨大的成果,促使美国食品和药物管理局 (FDA) 批准了四种针对 CD19 的 CAR-T 细胞产品。随着 CAR-T 细胞疗法在血液恶性肿瘤方面取得前所未有的成功,目前正在进行数百项临床前研究和临床试验,以探索将这种治疗方法转化为实体瘤。然而,非血液恶性肿瘤的临床经验并不那么令人鼓舞,只有少数患者获得完全缓解。肿瘤相关抗原异质性、CAR-T 细胞转运效率低下以及免疫抑制性肿瘤微环境被认为是实体瘤 CAR-T 细胞治疗的最关键障碍。

材料和方法:我们从 Pubmed 和 ClinicalTrials.gov 上查阅了关于 CAR-T 细胞免疫疗法治疗实体瘤的相关文献/临床试验。

结论:本文主要介绍了实体瘤 CAR-T 细胞临床试验的最新进展,重点介绍了已发表结果的研究。我们进一步讨论了 CAR-T 细胞疗法在实体瘤治疗中遇到的一些关键障碍,以及为克服这些障碍而采用的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/10129996/45fb7bf478e5/432_2022_4547_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/10129996/fb785b776fdb/432_2022_4547_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/10129996/49983c95a3dc/432_2022_4547_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/10129996/45fb7bf478e5/432_2022_4547_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/10129996/fb785b776fdb/432_2022_4547_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/10129996/49983c95a3dc/432_2022_4547_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/10129996/45fb7bf478e5/432_2022_4547_Fig3_HTML.jpg

相似文献

[1]
Comprehensive clinical evaluation of CAR-T cell immunotherapy for solid tumors: a path moving forward or a dead end?

J Cancer Res Clin Oncol. 2023-6

[2]
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[3]
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[4]
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[5]
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Front Immunol. 2018-7-31

[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]
Co-expression of IL-15/IL-15Ra complex enhances NKG2D-CAR T cell-mediated anti-pancreatic cancer immunity by activating the JAK/STAT5 signaling pathway.

Front Immunol. 2025-6-23

[2]
Advances in adoptive cell therapies in small cell lung cancer.

Explor Target Antitumor Ther. 2025-3-26

[3]
Tandem CAR-T cell therapy: recent advances and current challenges.

Front Immunol. 2025-2-28

[4]
Revolutionising Cancer Immunotherapy: Advancements and Prospects in Non-Viral CAR-NK Cell Engineering.

Cell Prolif. 2025-4

[5]
Gene Therapy: Towards a New Era of Medicine.

AAPS PharmSciTech. 2024-12-19

[6]
Revolutionizing cancer treatment: the emerging potential and potential challenges of self-processed CAR cell therapy.

Theranostics. 2024-10-28

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

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

[8]
CAR-T therapy for gastrointestinal cancers: current status, challenges, and future directions.

Braz J Med Biol Res. 2024

[9]
CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors.

Cell Mol Immunol. 2024-10

[10]
CAR-T Cell Therapy in Pancreatic and Biliary Tract Cancers: An Updated Review of Clinical Trials.

J Gastrointest Cancer. 2024-9

本文引用的文献

[1]
Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma.

Cancer Res Commun. 2023-5

[2]
PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial.

Nat Med. 2022-4

[3]
CAR-based therapies: opportunities for immuno-medicine beyond cancer.

Nat Metab. 2022-2

[4]
Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial.

Lung Cancer. 2022-3

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Hallmarks of Cancer: New Dimensions.

Cancer Discov. 2022-1

[6]
Emerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy.

Int J Mol Sci. 2021-11-9

[7]
CAR T-Cell Therapy in Hematological Malignancies.

Int J Mol Sci. 2021-8-20

[8]
IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin.

J Hematol Oncol. 2021-7-29

[9]
Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis.

Nat Med. 2021-9

[10]
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

Lancet. 2021-7-24

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