A novel TREM1/DAP12-based multiple chain CAR-T cell targets PTK7 in ovarian cancer therapy

• DOI: 10.1007/s12032-023-02084-9
• Publication Date: 2023-07-05T13:01:50Z
• Authors: Tongpeng Xu; Chen Wang; Xiaoyan Wang; Enxiu Wang; Bo Wang; Ming Sun
• Keywords: Ovarian Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Cell Line, Tumor; Humans; Receptor Protein-Tyrosine Kinases; Female; Immunotherapy, Adoptive; Xenograft Model Antitumor Assays; Cell Adhesion Molecules; Triggering Receptor Expressed on Myeloid Cells-1; 3. Good health

While CAR-T cell therapy has shown success against hematological tumors, its effectiveness for solid tumors, including ovarian cancer, remains unsatisfactory. This study aimed to develop and evaluate the efficacy of novel chimeric antigen receptor T (CAR-T) cells targeting PTK7 through TREM1/DAP12 signaling against ovarian cancer. The expression of PTK7 in ovarian cancer tissues and cells was evaluated using immunohistochemical staining and flow cytometric analysis. The anti-tumor effects of PTK7 CAR-T cells were assessed in vitro using real-time cell analysis and enzyme-linked immunosorbent assay, and in vivo using a xenograft tumor model. PTK7 was significantly expressed in ovarian cancer tissues and cells. PTK7-targeting CAR-T cells based on TREM1/DAP12 signaling exhibited potent cytotoxicity against ovarian cancer cells expressing PTK7 in vitro, and effectively eradicated tumors in vivo. Our findings suggest that TREM1/DAP12-based PTK7 CAR-T cells have potential as a treatment strategy for ovarian cancer. Further studies are needed to evaluate the safety and efficacy of this approach in clinical trials.