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工程学助力成功：改善嵌合抗原受体 T 细胞疗法治疗实体瘤的方法。

Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors.

机构信息

Immatics US, Inc, Houston, TX, 77030, USA.

Department of Bone Marrow Transplantation and Cellular Therapy, St Jude Children's Research Hospital, 262 Danny Thomas Place, MS321, Memphis, TN, 38105, USA.

出版信息

Drugs. 2019 Mar;79(4):401-415. doi: 10.1007/s40265-019-01071-7.

DOI:10.1007/s40265-019-01071-7
PMID:30796733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6613829/
Abstract

While impressive clinical responses have been observed using chimeric antigen receptor (CAR) T cells targeting CD19+ hematologic malignancies, limited clinical benefit has been observed using CAR T cells for a variety of solid tumors. Results of clinical studies have highlighted several obstacles which CAR T cells face in the context of solid tumors, including insufficient homing to tumor sites, lack of expansion and persistence, encountering a highly immunosuppressive tumor microenvironment, and heterogeneous antigen expression. In this review, we review clinical outcomes and discuss strategies to improve the antitumor activity of CAR T cells for solid tumors.

摘要

虽然使用嵌合抗原受体 (CAR) T 细胞靶向 CD19+血液系统恶性肿瘤已经观察到令人印象深刻的临床反应，但使用 CAR T 细胞治疗各种实体瘤的临床获益有限。临床研究结果强调了 CAR T 细胞在实体瘤环境中面临的几个障碍，包括向肿瘤部位归巢不足、缺乏扩增和持久性、遇到高度免疫抑制的肿瘤微环境以及抗原表达异质性。在这篇综述中，我们回顾了临床结果，并讨论了提高 CAR T 细胞治疗实体瘤抗肿瘤活性的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/03a1212e3508/40265_2019_1071_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/42da8aeab5ee/40265_2019_1071_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/4583fd0bffe6/40265_2019_1071_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/1c0e1fef8aaf/40265_2019_1071_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/03a1212e3508/40265_2019_1071_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/42da8aeab5ee/40265_2019_1071_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/4583fd0bffe6/40265_2019_1071_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/1c0e1fef8aaf/40265_2019_1071_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/7102133/03a1212e3508/40265_2019_1071_Fig4_HTML.jpg

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Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors.

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引用本文的文献

[1]
Car T Cells in Solid Tumors: Overcoming Obstacles.

Int J Mol Sci. 2024-4-10

[2]
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[4]
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[5]
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[6]
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[7]
IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities.

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[8]
The Application of CAR-T Cells in Haematological Malignancies.

Arch Immunol Ther Exp (Warsz). 2020-11-6

[9]
The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations.

J Pharm Sci. 2020-12

[10]
Rewriting History: Epigenetic Reprogramming of CD8 T Cell Differentiation to Enhance Immunotherapy.

Trends Immunol. 2020-8

本文引用的文献

[1]
Chimeric antigen receptor T cell immunotherapy for multiple myeloma: A review of current data and potential clinical applications.

Am J Hematol. 2019-2-25

[2]
Metabolic regulation of CAR T cell function by the hypoxic microenvironment in solid tumors.

Immunotherapy. 2019-3

[3]
Naïve T-cell Deficits at Diagnosis and after Chemotherapy Impair Cell Therapy Potential in Pediatric Cancers.

Cancer Discov. 2019-1-10

[4]
Chimeric Antigen Receptor Signaling Domains Differentially Regulate Proliferation and Native T Cell Receptor Function in Virus-Specific T Cells.

Front Med (Lausanne). 2018-12-11

[5]
Eradication of Neuroblastoma by T Cells Redirected with an Optimized GD2-Specific Chimeric Antigen Receptor and Interleukin-15.

Clin Cancer Res. 2019-1-7

[6]
Preclinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22.

Mol Ther Oncolytics. 2018-11-6

[7]
Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia.

Clin Cancer Res. 2018-9-6

[8]
Targeting T Cell Metabolism for Improvement of Cancer Immunotherapy.

Front Oncol. 2018-8-3

[9]
Targeting adenosine for cancer immunotherapy.

J Immunother Cancer. 2018-6-18

[10]
CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial.

Oncoimmunology. 2018-5-7

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