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Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma.

作者信息

Bughda Reyisa, Dimou Paraskevi, D'Souza Reena R, Klampatsa Astero

机构信息

Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.

出版信息

Immunotargets Ther. 2021 Aug 5;10:313-323. doi: 10.2147/ITT.S291767. eCollection 2021.


DOI:10.2147/ITT.S291767
PMID:34386436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8354246/
Abstract

Fibroblast activation protein (FAP) is a membrane protease that is highly expressed by cancer-associated fibroblasts (CAFs). FAP can modulate the tumor microenvironment (TME) by remodeling the extracellular matrix (ECM), and its overexpression on CAFs is associated with poor prognosis in various cancers. The TME is in part accountable for the limited efficacy of chimeric antigen receptor (CAR)-T cell therapy in treatment of solid tumors. Targeting FAP with CAR-T cells is one of the strategies being researched to overcome the challenges in the TME. This review describes the role of FAP in the TME and its potential as a target in CAR-T cell immunotherapy, summarizes the preclinical studies and clinical trials of anti-FAP-CAR-T cells to date, and reviews possible optimizations to augment their cytotoxic efficiency in solid tumors.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1618/8354246/6e0f152acf5d/ITT-10-313-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1618/8354246/3491bb2a2598/ITT-10-313-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1618/8354246/6e0f152acf5d/ITT-10-313-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1618/8354246/3491bb2a2598/ITT-10-313-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1618/8354246/6e0f152acf5d/ITT-10-313-g0002.jpg

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[3]
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[5]
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[7]
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[8]
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[9]
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[10]
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MedComm (2020). 2025-7-11

本文引用的文献

[1]
SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.

Sci Transl Med. 2021-4-28

[2]
Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy.

Biologics. 2021-4-14

[3]
Brexucabtagene autoleucel for the treatment of relapsed/refractory mantle cell lymphoma.

Expert Opin Biol Ther. 2021-4

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Biomark Res. 2020-11-11

[5]
Overcoming stromal barriers to immuno-oncological responses via fibroblast activation protein-targeted therapy.

Immunotherapy. 2021-2

[6]
Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations.

Ann Pharmacother. 2021-4

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Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma.

Ann Pharmacother. 2021-3

[8]
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape.

Front Immunol. 2020

[9]
A guide to cancer immunotherapy: from T cell basic science to clinical practice.

Nat Rev Immunol. 2020-5-20

[10]
Current Progress in CAR-T Cell Therapy for Solid Tumors.

Int J Biol Sci. 2019-9-7

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