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患者来源的膀胱癌类器官模型用于预测定制精准治疗的敏感性和可行性。

Patient-derived bladder cancer organoid model to predict sensitivity and feasibility of tailored precision therapy.

作者信息

Jiang Ying, Sun Xun, Song Xiaoyun, Li Zhen, Zhang Ping, Zhang Wen, Tang Dongqi

机构信息

Center for Gene and Immunotherapy, The Second Hospital of Shandong University, Cheeloo College of Medicine, Jinan, China.

Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan, China.

出版信息

Curr Urol. 2023 Dec;17(4):221-228. doi: 10.1097/CU9.0000000000000219. Epub 2023 Jul 20.

Abstract

BACKGROUND

Bladder cancer is a common and highly heterogeneous malignant tumor with a relatively poor prognosis. Thus, personalized treatment strategies for bladder cancer are essential for improving patient outcomes.

MATERIALS AND METHODS

We developed an efficient 3-dimensional in vitro organoid culture system for bladder cancer organoids (BCOs), which maintains the homology with the original patient tumors and the heterogeneity between different individuals. In addition, we constructed chimeric antigen receptor (CAR)-T cells targeting B7H3 and evaluated the antitumor function of CAR-T cells by coculturing them with BCOs.

RESULTS

The BCOs closely resembled the characteristics of human tumors and were used to test individual sensitivity to platinum-based drugs and olaparib therapy. Coculture with CAR-T cells demonstrated specific antigen recognition and immune activation, indicating their potential in immunotherapy.

CONCLUSIONS

Our study highlights the potential of BCOs to facilitate the development of personalized medicine for bladder cancer and improve the efficiency of drug discovery for bladder cancer therapy.

摘要

背景

膀胱癌是一种常见且高度异质性的恶性肿瘤,预后相对较差。因此,膀胱癌的个性化治疗策略对于改善患者预后至关重要。

材料与方法

我们开发了一种高效的三维体外类器官培养系统用于膀胱癌类器官(BCOs),该系统保持了与原始患者肿瘤的同源性以及不同个体之间的异质性。此外,我们构建了靶向B7H3的嵌合抗原受体(CAR)-T细胞,并通过将其与BCOs共培养来评估CAR-T细胞的抗肿瘤功能。

结果

BCOs与人类肿瘤的特征高度相似,用于测试个体对铂类药物和奥拉帕利治疗的敏感性。与CAR-T细胞共培养显示出特异性抗原识别和免疫激活,表明它们在免疫治疗中的潜力。

结论

我们的研究突出了BCOs在促进膀胱癌个性化医学发展以及提高膀胱癌治疗药物发现效率方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c01/10662868/dab163dad5c8/curr-urol-17-221-g001.jpg

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