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用于胆管癌治疗的 CAR-T 疗法与个体化疫苗开发:当前进展、作用机制与挑战

英文原题:Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.

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Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.

PubMed 2024/12/14(内容时间) Am J Pathol Q1 · IF 4.9(JCR 2025)

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中文摘要

胆管癌(CCA)是一种致死率极高且发病率上升的恶性肿瘤,死亡率高、总生存期短,且对传统放化疗应答有限。靶向特定基因突变的疗法扩大了部分患者的治疗选择。嵌合抗原受体修饰T细胞(CAR-T)免疫疗法和个体化疫苗的引入,为多种癌症的管理开辟新途径。研究者已投入大量精力开展免疫治疗临床前研究和临床试验,方法包括CAR-T 疗法、疫苗及抗体类疗法(如抗体药物偶联物)。然而,CAR-T 疗法和疫苗治疗晚期不可切除/转移性胆管癌的潜力尚未得到充分探索。本文概述抗体类免疫疗法在胆管癌治疗中的现状,尤其聚焦CAR-T 疗法和疫苗,并提出CAR-T 和疫苗靶点选择框架,阐述有前景可靶向抗原的生物学特征及未来潜在治疗靶点。

展开英文摘要原文

Cholangiocarcinoma (CCA) is a highly fatal malignancy with an increasing prevalence, a high mortality rate, poor overall survival, and limited responsiveness to conventional chemoradiotherapy. Targeted therapies addressing specific gene mutations have expanded treatment options for some patient populations.

The introduction of chimeric antigen receptor-modified T-cell (CAR-T) immunotherapy and personalized vaccines have opened up a new avenue for managing various cancers. Considerable efforts have been dedicated to preclinical research and ongoing clinical trials of immunotherapeutic approaches including CAR-T therapy, vaccines, and antibody-based therapies such as antibody drug conjugates.

However, the potential of CAR-T therapy and vaccines in treating advanced unresectable/metastatic cholangiocarcinoma remains largely unexplored. This article offers an overview of the current landscape of antibody-based immunotherapy, particularly CAR-T therapy and vaccines in the context of cholangiocarcinoma treatment. It outlines a framework for selecting CAR-T and vaccine targets and delves into the biology of promising targetable antigens, as well as potential future therapeutic targets.

论文信息

作者
Li D、Andaloori L、Crowe M、Lin S、Hong J、Zaidi N、Ho M
第一作者单位
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.United States
通讯作者单位
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. Electronic address: homi@mail.nih.gov.United States
文献类型
综述
期刊
The American journal of pathology2025 Mar
原文标识
PubMed 39675505 · DOI 10.1016/j.ajpath.2024.10.021