Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Osaka, Japan.
Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan.
Cancer Sci. 2024 Nov;115(11):3532-3542. doi: 10.1111/cas.16285. Epub 2024 Aug 21.
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.
随着肿瘤免疫治疗的最新进展,嵌合抗原受体 T(CAR-T)细胞疗法在几种血液肿瘤中取得了前所未有的成功,显著改善了患者的预后。然而,在实体瘤中,由于抗原不确定性高和肿瘤微环境(TME)极其受限,CAR-T 细胞疗法的疗效受到限制。这一挑战促使人们探索新的靶点,其中成纤维细胞激活蛋白(FAP)因其在各种实体瘤的 TME 中相对稳定和特异性表达而受到关注,使其成为 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,并探讨了其在 CAR-T 细胞疗法中的潜在应用,包括靶向 FAP 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。还探讨了该治疗策略的挑战和未来优化方向,为 CAR-T 细胞疗法在实体瘤中的应用提供了新的视角和策略。
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