3D Scaffold-Based Culture System Enhances Preclinical Evaluation of Natural Killer Cell Therapy in A549 Lung Cancer Cells.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-11-18 Epub Date: 2024-10-11 DOI:10.1021/acsabm.4c00800
Eun Hee Han, Sun-Hee Cho, Sang Nam Lee, Mi Young Cho, Hyunseung Lee, Soo Yun Lee, Chau Ngoc Thi Tran, Hye Sun Park, Jin Young Min, Hye Min Kim, Min Sung Park, Tae-Don Kim, Yong Taik Lim, Kwan Soo Hong
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Abstract

Cell-based immunotherapies have emerged as promising cancer treatment modalities, demonstrating remarkable clinical efficacy. As interest in applying immune cell-based therapies to solid tumors has gained momentum, experimental models that enable long-term monitoring and mimic clinical administration are increasingly necessary. This study explores the potential of scaffold-based cell culture technologies, specifically three-dimensional (3D) extracellular matrix (ECM)-like frameworks, as promising solutions. These frameworks facilitate unhindered immune cell growth and enable continuous cancer cell culture. The three-dimensional (3D) cell culture model was developed using tailored scaffolds for natural killer (NK) cell culture. Within this framework, A549 lung cancer cells were cocultured with NK cells, allowing real-time monitoring for up to 28 days. The expression of critical markers associated with anticancer drug resistance and epithelial-mesenchymal transition (EMT) was evaluated in cancer cells within this 3D culture context. Compared to conventional 2D monolayer cultures, this 3D scaffold-based culture revealed that solid tumor cells, specifically A549 cells, exhibited heightened resistance to anticancer drugs. Additionally, the 3D culture environment upregulated the expression of EMT markers namely vimentin, N-cadherin, and fibronectin, while NK and zEGFR-CAR-NK cells displayed anticancer effects. In the two-dimensional (2D) coculture, only zEGFR-CAR-NK cells exhibited such effects in the 3D coculture system, highlighting an intriguing inconsistency with the 2D culture model, further confirmed by in vivo experiments. This in vitro 3D cell culture model reliably predicts outcomes in NK immunotherapy experiments. Thus, it represents a valuable tool for investigating drug resistance mechanisms and assessing the efficacy of immune cell-based therapies. By bridging the gap between in vitro and in vivo investigations, this model effectively translates potential treatments into animal models and facilitates rigorous preclinical evaluations.

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基于三维支架的培养系统增强了自然杀伤细胞疗法在 A549 肺癌细胞中的临床前评估。
以细胞为基础的免疫疗法已成为一种很有前途的癌症治疗方式,临床疗效显著。随着人们对将基于免疫细胞的疗法应用于实体瘤的兴趣日渐浓厚,能够进行长期监测和模拟临床用药的实验模型越来越有必要。本研究探讨了基于支架的细胞培养技术的潜力,特别是三维(3D)细胞外基质(ECM)样框架,将其作为有前途的解决方案。这些框架可促进免疫细胞不受阻碍地生长,并实现连续的癌细胞培养。三维(3D)细胞培养模型是利用为自然杀伤(NK)细胞培养量身定制的支架开发的。在此框架内,A549 肺癌细胞与 NK 细胞共同培养,可进行长达 28 天的实时监测。在这种三维培养环境中,对癌细胞中与抗癌药物耐药性和上皮-间质转化(EMT)相关的关键标记物的表达进行了评估。与传统的二维单层培养相比,这种基于三维支架的培养发现实体瘤细胞,特别是 A549 细胞,对抗癌药物的耐药性增强。此外,三维培养环境还上调了EMT标记物(即波形蛋白、N-粘连蛋白和纤连蛋白)的表达,而NK和zEGFR-CAR-NK细胞则显示出抗癌效果。在二维(2D)共培养中,只有zEGFR-CAR-NK细胞在三维共培养系统中表现出这种效应,这凸显了二维培养模型与三维共培养模型之间令人费解的不一致,体内实验进一步证实了这一点。这种体外三维细胞培养模型能可靠地预测 NK 免疫疗法实验的结果。因此,它是研究耐药机制和评估免疫细胞疗法疗效的重要工具。通过弥合体外和体内研究之间的差距,该模型能有效地将潜在的治疗方法转化为动物模型,并促进严格的临床前评估。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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