德国图宾根大学Peter Loskill和维尔茨堡大学Miriam Alb研究组合作研发了，用于测试嵌合抗原受体（CAR）-T细胞疗效特异性和安全性的乳腺癌芯片。2024年5月15日，国际学术期刊《细胞-干细胞》发表了这一成果。

据了解，CAR-T 细胞领域非常需要能在生理上重现实体瘤和肿瘤微环境（TME）的相关人体模型。

研究人员研发了一种涵盖内皮屏障的乳腺癌芯片模型，灌注的免疫细胞能迁移、浸润到肿瘤中，并在长达8天的灌注培养过程中同时监测细胞因子的释放。研究人员证明了它在研究CAR-T细胞治疗方面的用途，以及通过药物控制免疫反应的能力。

此外，研究还整合了原发性乳腺癌器官组织来研究患者特异性CAR-T细胞的疗效。该肿瘤芯片的模块化结构为研究TME中其他细胞类型的作用铺平了道路，证明了其在科研到临床转化应用中的潜力，并加速CAR-T细胞产品的临床前研发。

附：英文原文

Title: Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells

Author: Tengku Ibrahim Maulana, Claudia Teufel, Madalena Cipriano, Julia Roosz, Lisa Lazarevski, Francijna E. van den Hil, Lukas Scheller, Valeria Orlova, André Koch, Michael Hudecek, Miriam Alb, Peter Loskill

Issue&Volume: 2024-05-15

Abstract: Physiologically relevant human models that recapitulate the challenges of solid tumors and the tumor microenvironment (TME) are highly desired in the chimeric antigen receptor (CAR)-T cell field. We developed a breast cancer-on-chip model with an integrated endothelial barrier that enables the transmigration of perfused immune cells, their infiltration into the tumor, and concomitant monitoring of cytokine release during perfused culture over a period of up to 8 days. Here, we exemplified its use for investigating CAR-T cell efficacy and the ability to control the immune reaction with a pharmacological on/off switch. Additionally, we integrated primary breast cancer organoids to study patient-specific CAR-T cell efficacy. The modular architecture of our tumor-on-chip paves the way for studying the role of other cell types in the TME and thus provides the potential for broad application in bench-to-bedside translation as well as acceleration of the preclinical development of CAR-T cell products.

DOI: 10.1016/j.stem.2024.04.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00145-0