CELL INTELLIGENCE · 肿瘤细胞治疗研究

CELLIN 肿瘤细胞治疗研究

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3D 生物打印血管化乳腺肿瘤模型上的化疗药物与 CAR-T 细胞免疫治疗药物筛选

英文原题：Chemotherapeutics and CAR-T Cell-Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor Model.

查看英文原题

Chemotherapeutics and CAR-T Cell-Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor Model.

PubMed 2022/10/03（内容时间） Adv Funct Mater Q1 · IF 19.9（JCR 2025）

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靶点：HER2技术：CAR-T地区：美国
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中文摘要

癌症治疗虽已显著进步，但缺乏标准化且具生理相关性的体外测试平台，限制了抗癌药物早期筛选。肿瘤微环境与免疫应答之间的复杂相互作用是主要障碍。为应对这一问题，研究者开发了一种动态流动式3D生物打印多尺度血管化乳腺肿瘤模型，可用于评估化疗和免疫治疗。异质性肿瘤被精确打印在距灌流血管预设的位置，并表现出肿瘤血管生成及癌细胞侵入灌流血管的现象。生物打印肿瘤经不同剂量多柔比星处理72小时后呈现剂量依赖性药物反应。更重要的是，研究通过灌流HER2靶向嵌合抗原受体（CAR）改造的CD8+ T细胞24或72小时，探索细胞免疫治疗。CAR-T 大量募集至内皮，显著活化并浸润肿瘤部位，肿瘤体积最多降低70%。该平台为未来将抗癌疗法转化至精准医疗提供稳健、精确制造且具生理相关性的肿瘤模型。

展开英文摘要原文

Despite substantial advancements in development of cancer treatments, lack of standardized and physiologically-relevant in vitro testing platforms limit the early screening of anticancer agents. A major barrier is the complex interplay between the tumor microenvironment and immune response. To tackle this, a dynamic-flow based 3D bioprinted multi-scale vascularized breast tumor model, responding to chemo and immunotherapeutics is developed. Heterotypic tumors are precisely bioprinted at pre-defined distances from a perfused vasculature, exhibit tumor angiogenesis and cancer cell invasion into the perfused vasculature.

Bioprinted tumors treated with varying dosages of doxorubicin for 72 h portray a dose-dependent drug response behavior. More importantly, a cell based immune therapy approach is explored by perfusing HER2-targeting chimeric antigen receptor (CAR) modified CD8 + T cells for 24 or 72 h.

Extensive CAR-T cell recruitment to the endothelium, substantial T cell activation and infiltration to the tumor site, resulted in up to 70% reduction in tumor volumes. The presented platform paves the way for a robust, precisely fabricated, and physiologically-relevant tumor model for future translation of anti-cancer therapies to personalized medicine.

论文信息

作者
Dey M、Kim MH、Dogan M、Nagamine M、Kozhaya L、Celik N、Unutmaz D、Ozbolat IT
第一作者单位
Department of Chemistry, Penn State University, University Park, PA 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA 16802, USA.United States
通讯作者单位
The Huck Institutes of the Life Sciences, Penn State University, University Park, PA 16802, USA; Biomedical Engineering Department, Penn State University, University Park, PA 16802, USA; Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA; Materials Research Institute, Penn State University, University Park, PA 16802, USA; Cancer Institute, Penn State University, Hershey, PA 17033, USA; Neurosurgery Department, Penn State University, Hershey, PA 17033, USA; Department of Medical Oncology, Cukurova University, Adana 01330, Turkey.United States
期刊
Advanced functional materials2022 Dec 22
原文标识
PubMed 38938621　·　DOI 10.1002/adfm.202203966

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