CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:In Vitro 3D Models of Haematological Malignancies: Current Trends and the Road Ahead?
In Vitro 3D Models of Haematological Malignancies: Current Trends and the Road Ahead?
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血液系统恶性肿瘤包括一组多样化的危及生命的全身性疾病,包括白血病、淋巴瘤和多发性骨髓瘤。目前可用的疗法,包括化疗、免疫治疗和 CAR-T 细胞,往往伴随着重要的副作用以及耐药性的产生,进而导致疾病复发。在过去几十年中,大量研究证明肿瘤微环境显著影响癌细胞增殖和肿瘤对治疗的反应。仿生体外模型的开发可能促进对癌细胞与肿瘤微环境之间相互作用的研究,并有助于更好地理解导致耐药性的机制。尽管先进的体外模型在实体瘤领域已得到广泛探索,但由于血液肿瘤微环境的复杂性,血液系统恶性肿瘤的模拟主要依赖于较为简单的系统,通常局限于二维细胞培养——这从本质上排除了微环境生态位——或依赖于存在伦理争议的动物模型。本综述旨在报告血液系统恶性肿瘤 3D 体外模型的最新概况,强调现有系统的关键特征和局限性,以启发这一未被充分探索领域的进一步研究。
Haematological malignancies comprise a diverse group of life-threatening systemic diseases, including leukaemia, lymphoma, and multiple myeloma. Currently available therapies, including chemotherapy, immunotherapy, and CAR-T cells, are often associated with important side effects and with the development of drug resistance and, consequently, disease relapse. In the last decades, it was largely demonstrated that the tumor microenvironment significantly affects cancer cell proliferation and tumor response to treatment. The development of biomimetic, in vitro models may promote the investigation of the interactions between cancer cells and the tumor microenvironment and may help to better understand the mechanisms leading to drug resistance.
Although advanced in vitro models have been largely explored in the field of solid tumors, due to the complex nature of the blood cancer tumor microenvironment, the mimicking of haematological malignancies mostly relies on simpler systems, often limited to two-dimensional cell culture, which intrinsically excludes the microenvironmental niche, or to ethically debated animal models.
This review aims at reporting an updated overview of state-of-the-art hematological malignancies 3D in vitro models, emphasizing the key features and limitations of existing systems to inspire further research in this underexplored field.
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