A frequent symptom of metastasized breast cancer (BC) includes the development of malignant pleural effusion (MPE), which contains malignant cells derived from the primary tumor site. The poor prognosis of MPE in metastasized BC indicates the necessity for dependable precision oncology and the importance of models representing the heterogenous nature of metastatic BC. In this study, we cultured MPE-derived metastatic tumor cells from four advanced BC patients using organoid technology. We assessed the expression of tumor-associated antigens on MPE-derived organoid lines by flow cytometry (FC). Based on an individual antigen expression pattern, patient-derived organoids were treated with adapter CAR-T cells (AdCAR-T) and biotinylated monoclonal antibodies targeting CD276, HER2, EGFR, TROP2, or EpCAM. Co-culture assays revealed specific organoid lysis by AdCAR-T depending on individual antigen expression patterns. Our results demonstrate that MPE-derived organoids can serve as a reliable tool for assessing the efficacy of AdCAR-T on metastatic BC in a patient-individualized manner. This approach could potentially be applied in a preclinical setting to instruct therapy decisions. Further, our study demonstrates the feasibility of precision immunotherapy utilizing AdCAR-T to target patient-individualized antigen patterns.
转移性乳腺癌（BC）的常见症状之一是恶性胸腔积液（MPE）的形成，其中含有源自原发肿瘤部位的恶性细胞。MPE在转移性BC中的不良预后表明，需要可靠的精准肿瘤学方法，并突显了能够体现转移性BC异质性特征模型的重要性。在本研究中，我们利用类器官技术培养了四名晚期BC患者的MPE来源转移性肿瘤细胞。通过流式细胞术（FC）评估了MPE来源类器官系中肿瘤相关抗原的表达情况。基于个体抗原表达谱，我们采用适配性CAR-T细胞（AdCAR-T）及靶向CD276、HER2、EGFR、TROP2或EpCAM的生物素化单克隆抗体对患者来源类器官进行处理。共培养实验显示，AdCAR-T对类器官的特异性裂解作用取决于个体抗原表达模式。我们的研究结果表明，MPE来源类器官可作为评估AdCAR-T对转移性BC疗效的可靠工具，且具有患者个体化特性。该方法有望应用于临床前研究以指导治疗决策。此外，本研究证实了利用AdCAR-T靶向患者个体化抗原模式进行精准免疫治疗的可行性。
肿瘤(癌症)患者之家