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在瘤微环境的重建3D细胞模型中评估基于抗体的新型疗法

Giacomo Domenici^1,2, Nuno F Lopes^1,2, Gonçalo Trindade^1,2

¹iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2780-901, Portugal.

Advanced biology

|November 27, 2024

概括

一个新的3D乳腺癌模型 (3D-3) 有效模拟瘤微环境 (TME). 该模型准确评估抗体-药物合物 (ADC) 和针对瘤和免疫细胞的免疫调节抗体.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
生物材料科学生物材料科学

背景情况:

针对性疗法,如抗体药物合物 (ADC) 和免疫调节抗体 (Abs),对于癌症治疗至关重要.
评估这些疗法需要模拟复杂瘤微环境 (TME) 的临床前模型.

研究的目的:

开发一个3D乳腺癌细胞模型 (3D-3) 总结TME的关键特征.
评估3D-3模型对评估基于抗体的治疗方法的有用性.

主要方法:

使用酸盐和基于化的培养的微封装策略被用于创建3D-3模型.
流体 (癌症相关纤维细胞 - CAF) 和免疫 (瘤相关巨细胞 - TAM) 组件被纳入多细胞瘤球体.
该模型的疗效使用抗HER2抗体-药物合物 (ADC) 和阻断抗体的殖民地刺激因子1受体 (CSF1R) 进行了测试.

主要成果:

ADCs证明了针对HER2+乳腺癌球体的瘤细胞特异性细胞毒性,节省了HER2-阴性CAFs.
阻断CSF1R的抗体减少了TAM中的免疫抑制标记物,反映了体内观察.
3D-3模型成功模拟了癌细胞,CAF和TAM之间的相互作用.

结论:

基于人类TME的3D-3细胞模型是评估基于抗体的新疗法的宝贵工具.
该模型可以评估针对TME内的癌细胞和巨细胞的治疗方法的抗瘤和免疫调节潜力.

关键词:

3D癌症模型 3D癌症模型抗体与药物结合物的结合物.与癌症相关的纤维细胞.有针对性的治疗方法.与瘤相关的巨细胞.

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