Neuroblastoma and DIPG Organoid Coculture System for Personalized Assessment of Novel Anticancer Immunotherapies.
Neuroblastoma and DIPG Organoid Coculture System for Personalized Assessment of Novel Anticancer Immunotherapies.
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神经母细胞瘤和DIPG器官共培养系统，用于对新型抗癌免疫疗法的个性化评估。
DOI：
10.3390/jpm11090869
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发表时间：
2021-08-30
影响因子：
--
通讯作者：
Molenaar JJ
中科院分区：
文献类型：
--
作者：
M Kholosy W;Derieppe M;van den Ham F;Ober K;Su Y;Custers L;Schild L;M J van Zogchel L;M Wellens L;R Ariese H;Szanto CL;Wienke J;Dierselhuis MP;van Vuurden D;Dolman EM;Molenaar JJ
癌症免疫治疗已经改变了成人癌症治疗的前景，并为治疗儿童恶性肿瘤带来了巨大的希望。然而，在体外测试共培养系统，以评估免疫治疗的代表性儿科肿瘤模型的疗效缺乏。在这里，我们描述了建立儿科肿瘤类器官和免疫细胞的离体测试共培养系统的详细程序，该系统能够评估儿科肿瘤类器官中的不同免疫治疗方法。我们提供了一个逐步的方案，用于使用确定的无血清培养基有效产生稳定表达eGFP-ffLuc转基因的患者来源的弥漫性内在脑桥胶质瘤（DIPG）和神经母细胞瘤类器官。与铬释放测定相比，新平台允许使用非放射性测定实时可视化，监测和稳健定量肿瘤类器官细胞的细胞毒性。为了评价该系统在儿科免疫肿瘤学领域药物检测中的实用性，我们使用临床上用于高危神经母细胞瘤儿童的免疫治疗策略dinutuximab（抗GD2单克隆抗体）对GD2有效和缺乏的患者源性神经母细胞瘤类器官进行了体外检测。我们使用人免疫细胞和儿科肿瘤类器官作为离体肿瘤模型，证明了我们的离体共培养系统的可行性和灵敏度。我们的研究为侵袭性儿科癌症（如神经母细胞瘤和DIPG）的潜在抗癌免疫疗法的个性化测试提供了一个新的平台。
Cancer immunotherapy has transformed the landscape of adult cancer treatment and holds a great promise to treat paediatric malignancies. However, in vitro test coculture systems to evaluate the efficacy of immunotherapies on representative paediatric tumour models are lacking. Here, we describe a detailed procedure for the establishment of an ex vivo test coculture system of paediatric tumour organoids and immune cells that enables assessment of different immunotherapy approaches in paediatric tumour organoids. We provide a step-by-step protocol for an efficient generation of patient-derived diffuse intrinsic pontine glioma (DIPG) and neuroblastoma organoids stably expressing eGFP-ffLuc transgenes using defined serum-free medium. In contrast to the chromium-release assay, the new platform allows for visualization, monitoring and robust quantification of tumour organoid cell cytotoxicity using a non-radioactive assay in real-time. To evaluate the utility of this system for drug testing in the paediatric immuno-oncology field, we tested our in vitro assay using a clinically used immunotherapy strategy for children with high-risk neuroblastoma, dinutuximab (anti-GD2 monoclonal antibody), on GD2 proficient and deficient patient-derived neuroblastoma organoids. We demonstrated the feasibility and sensitivity of our ex vivo coculture system using human immune cells and paediatric tumour organoids as ex vivo tumour models. Our study provides a novel platform for personalized testing of potential anticancer immunotherapies for aggressive paediatric cancers such as neuroblastoma and DIPG.
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影响因子：
3.7
作者：
Hennika T;Hu G;Olaciregui NG;Barton KL;Ehteda A;Chitranjan A;Chang C;Gifford AJ;Tsoli M;Ziegler DS;Carcaboso AM;Becher OJ
通讯作者：
Becher OJ
影响因子：
16.6
作者：
Calandrini, Camilla;Schutgens, Frans;Drost, Jarno
通讯作者：
Drost, Jarno
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
4
作者：
Wesierska-Gadek, J;Gueorguieva, M;Zerza-Schnitzhofer, G
通讯作者：
Zerza-Schnitzhofer, G
影响因子：
--
作者：
Wonderlich, John;Shearer, Gene;Presby, Matthew M
通讯作者：
Presby, Matthew M