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

被引：107
作者：
Bughda, Reyisa [1 ]
Dimou, Paraskevi [1 ]
D'Souza, Reena R. [1 ]
Klampatsa, Astero [1 ]
机构：
[1] Inst Canc Res, Div Canc Therapeut, London, England
来源：
IMMUNOTARGETS AND THERAPY | 2021年 / 10卷
关键词：
CAR T-cells; immunotherapy; tumor microenvironment; fibroblasts; fibroblast-activating-protein; solid tumors; stroma; CANCER-ASSOCIATED FIBROBLASTS; DIPEPTIDYL-PEPTIDASE; ANTIGEN RECEPTOR; EXPRESSION; BREAST; PROLIFERATION; ALPHA; IMMUNOTHERAPY; HETEROGENEITY; GROWTH;
D O I：
10.2147/ITT.S291767
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
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收藏
页码：313 / 323
页数：11
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