Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma.
Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma.
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DOI：
10.2147/itt.s291767
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发表时间：
2021
影响因子：
7.2
通讯作者：
Klampatsa A
中科院分区：
文献类型：
--
作者：
Bughda R;Dimou P;D'Souza RR;Klampatsa A
成纤维细胞激活蛋白 (FAP) 是一种膜蛋白酶，在癌症相关成纤维细胞 (CAF) 中高度表达。 FAP可以通过重塑细胞外基质（ECM）来调节肿瘤微环境（TME），其在CAF上的过度表达与多种癌症的不良预后相关。 TME 是嵌合抗原受体 (CAR)-T 细胞疗法在实体瘤治疗中疗效有限的部分原因。用 CAR-T 细胞靶向 FAP 是为克服 TME 挑战而正在研究的策略之一。这篇综述描述了 FAP 在 TME 中的作用及其作为 CAR-T 细胞免疫治疗靶点的潜力，总结了迄今为止抗 FAP-CAR-T 细胞的临床前研究和临床试验，并回顾了增强其在实体瘤中细胞毒性效率的可能优化。
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.