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肿瘤类器官和组装体:用于免疫治疗的患者来源癌症化身

英文原题:Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.

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Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.

PubMed 2024/04/01(内容时间) Clin Transl Med Q1 · IF 7.9(JCR 2025)

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研究概要

基础研究和临床试验正在进行中,目的是用这些模型替代动物。使用 PDTO 进行临床前免疫治疗筛选将有益于癌症患者。当前的 PDTO 模型尚未构建关键的细胞和非细胞成分。PDTO 应具有可扩展性和可编辑性。除非能够建立成熟的 PDTO,否则 PDTO 是有前景的免疫治疗临床前模型。迫切需要具有共识标准的 PDTO 生物样本库。

研究思路结论见上方概要

类器官技术是一个新兴且快速发展的领域,在研究器官发育和筛选治疗方案方面显示出前景。尽管类器官已被提出十年,但仍存在担忧,包括批次间差异、缺乏原生微环境和临床适用性。主体:类器官的概念衍生出患者来源的肿瘤类器官(PDTOs),用于个性化药物筛选和新药发现,降低用药不当的风险。PDTOs与原发性肿瘤的相似性越大,模型的影响力就越大。最近,受细胞共培养技术启发的“肿瘤组装体”引起了关注,以补充当前的PDTO技术。高质量的PDTOs必须重新组装关键组分,包括多种细胞类型、肿瘤基质、旁分泌因子、血管生成和微生物。本综述首先简要概述类器官和PDTOs的历史,然后介绍当前生成PDTOs和肿瘤组装体的方法。个性化药物筛选已被实践;然而,PDTOs能否预测免疫疗法仍不清楚,包括免疫药物(如免疫检查点抑制剂)和免疫细胞(如TIL(肿瘤浸润淋巴细胞)、T细胞受体工程T细胞和CAR-T 细胞)。PDTOs作为患者的癌症化身,可以扩增和储存以形成生物样本库。

展开英文摘要原文

Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank.

Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

论文信息

作者
Mei J、Liu X、Tian HX、Chen Y、Cao Y、Zeng J、Liu YC、Chen Y
单位
Oujiang Laboratory; Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, People's Republic of China.China
文献类型
综述 · 非美国政府资助研究
期刊
Clinical and translational medicine2024 Apr
原文标识
PubMed 38664597 · DOI 10.1002/ctm2.1656