工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor organoids targeted by receptor-engineered immune cells: A promising approach for advancing cancer immunotherapy.
Tumor organoids targeted by receptor-engineered immune cells: A promising approach for advancing cancer immunotherapy.
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患者来源肿瘤类器官(通常简称肿瘤类器官)可作为体外肿瘤模型,用于活体生物样本库建立、生物标志物鉴定、药物筛选和个体化精准医疗等肿瘤研究。尽管嵌合抗原受体(CAR)工程化T细胞治疗B细胞恶性肿瘤已取得巨大成功,受体工程化免疫细胞疗法治疗实体瘤的疗效仍不理想,原因包括肿瘤分子异质性和免疫抑制性肿瘤微环境。此外,由于药物或过继转移免疫细胞存在毒性,直接开展大规模临床研究受到限制。因此,需要利用类器官等更优的体外模型开展更多替代性研究,以鉴定肿瘤细胞上的靶分子或生物标志物。肿瘤类器官的三维结构和遗传特征可模拟实体瘤微环境,因此已成为评估受体工程化免疫细胞(EIC)疗效和毒性的合适体外模型。本综述总结近期利用肿瘤类器官创新和分析EIC癌症免疫治疗的进展,并重点介绍其局限性及未来潜在研究方向,以更好地评估和改善EIC癌症疗法。
Patient-derived tumor organoids, often referred to as tumor organoids, serve as in vitro tumor models for tumor-related research, such as living biobanks, identification of biomarkers, drug screening and personalized precision medicine. Despite great success of chimeric antigen receptor (CAR)-engineered T cell therapy of B cell malignancies, the efficacy of receptor-engineered immune cell therapy of solid tumors remains suboptimal due to the molecular heterogeneity and immunosuppressive tumor microenvironment.
Moreover, direct and extensive clinical studies are limited because of the toxicity of drugs or adoptively transferred immune cells.
Thus, more alternative studies using better in vitro models, such as organoids, are needed to identify the target molecules or biomarkers in tumor cells. Tumor organoids have emerged as a suitable in vitro model for evaluating therapeutic efficacy and toxicity of receptor-engineered immune cells (EICs), because 3D structure and genetic characteristics of tumor organoids mimic the solid tumor microenvironment.
In this review, we have summarized the recent advances in the application of tumor organoids for innovating and analyzing immunotherapy of cancers using EICs.
We have also highlighted their limitations and pinpointed the potential future research direction in order to better evaluate and improve EIC therapy of cancer.
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