Precision Immunotherapy Utilizing Adapter CAR-T Cells (AdCAR-T) in Metastatic Breast Cancer Leads to Target Specific Lysis

• Published in: Cancers Vol. 16; no. 1; p. 168
• Main Authors: Önder, Cansu E, Moustafa-Oglou, Moustafa, Schröder, Sarah M, Hartkopf, Andreas D, Koch, André, Seitz, Christian M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.12.2023; MDPI
• Subjects: Antigen (tumor-associated); Antigens; Biopsy; Breast cancer; Cancer therapies; Cell culture; Cells; ErbB-2 protein; Feasibility studies; Flow cytometry; Growth factors; Immunotherapy; Lymphocytes; Lymphocytes T; Lysis; Medical prognosis; Medical research; Medicine, Experimental; Metastases; Metastasis; Monoclonal antibodies; Oncology; Organoids; Patients; Pleural effusion; Precision medicine; Quality of life; Scientific equipment and supplies industry; T cells; Tumor cells; Tumors; Canada; United States; Massachusetts; Germany; United States > US; metastasis; adapter CAR-T cells; patient-derived organoids; breast cancer; cancer biology; organoid culture; precision immunotherapy; pleural effusion
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16010168

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.