Dadgar Neda, Arunachalam Arun K, Hong Hanna, Phoon Yee Peng, Arpi-Palacios Jorge E, Uysal Melis, Wehrle Chase J, Aucejo Federico, Ma Wen Wee, Melenhorst Jan Joseph
Cleveland Clinic Foundation, Enterprise Cancer Institute, Translational Hematology & Oncology Research, Cleveland, OH 44114, USA.
Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH 44195, USA.
Cancers (Basel). 2024 Sep 23;16(18):3232. doi: 10.3390/cancers16183232.
Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.
胆管癌(CCA)是一种起源于胆管的罕见且侵袭性强的恶性肿瘤,预后较差且治疗选择有限。传统疗法,如手术、化疗和放疗,疗效有限,尤其是在晚期病例中。免疫疗法的最新进展,特别是基于T细胞的疗法,如嵌合抗原受体T(CAR T)细胞、肿瘤浸润淋巴细胞(TIL)和基于T细胞受体(TCR)的疗法,为改善CCA的治疗结果开辟了新途径。本综述全面概述了CCA的T细胞疗法现状,重点关注CAR T细胞疗法。它突出了关键挑战,包括复杂的肿瘤微环境和免疫逃逸机制,以及临床前和临床试验取得的进展。该综述还讨论了针对特定CCA抗原(如MUC1、EGFR和CD133)的正在进行的临床试验,以及精准免疫疗法在提高治疗效果方面不断演变的作用。尽管取得了重大进展,但仍需要进一步研究以优化这些针对CCA等实体瘤的疗法。通过总结最新的临床结果和未来方向,本综述强调了T细胞疗法在彻底改变CCA治疗方面的广阔潜力。