Fibroblast activation protein constitutes a novel target of chimeric antigen receptor T-cell therapy in solid tumors

IF 4.5 2区 医学 Q1 ONCOLOGY Cancer Science Pub Date : 2024-08-21 DOI:10.1111/cas.16285
Sikun Meng, Tomoaki Hara, Yutaka Miura, Hideshi Ishii
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Abstract

With recent advances in tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has achieved unprecedented success in several hematologic tumors, significantly improving patient prognosis. However, in solid tumors, the efficacy of CAR-T cell therapy is limited because of high antigen uncertainty and the extremely restrictive tumor microenvironment (TME). This challenge has led to the exploration of new targets, among which fibroblast activation protein (FAP) has gained attention for its relatively stable and specific expression in the TME of various solid tumors, making it a potential new target for CAR-T cell therapy. This study comprehensively analyzed the biological characteristics of FAP and discussed its potential application in CAR-T cell therapy, including the theoretical basis, and preclinical and clinical research progress of targeting FAP with CAR-T cell therapy for solid tumor treatment. The challenges and future optimization directions of this treatment strategy were also explored, providing new perspectives and strategies for CAR-T cell therapy in solid tumors.

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成纤维细胞活化蛋白是嵌合抗原受体 T 细胞疗法治疗实体瘤的新靶点。
随着肿瘤免疫疗法的最新进展,嵌合抗原受体 T(CAR-T)细胞疗法在多种血液肿瘤中取得了前所未有的成功,大大改善了患者的预后。然而,在实体瘤中,由于抗原的高度不确定性和肿瘤微环境(TME)的极端限制性,CAR-T 细胞疗法的疗效受到了限制。这一挑战引发了人们对新靶点的探索,其中成纤维细胞活化蛋白(FAP)因其在各种实体瘤TME中相对稳定和特异性的表达而备受关注,成为CAR-T细胞疗法的潜在新靶点。本研究全面分析了FAP的生物学特性,探讨了其在CAR-T细胞疗法中的潜在应用,包括以FAP为靶点的CAR-T细胞疗法治疗实体瘤的理论基础、临床前和临床研究进展。同时还探讨了该治疗策略面临的挑战和未来的优化方向,为CAR-T细胞治疗实体瘤提供了新的视角和策略。
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来源期刊
Cancer Science
Cancer Science 医学-肿瘤学
自引率
3.50%
发文量
406
审稿时长
2 months
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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