Abstract P28: Synergistic Anti-Tumor Effects of Metastatic Ovarian Cancer on Combinatory Treatment with Chemotherapy and Metronomic CHI3L1-Specific Antibody Radionuclide

Background: Radionuclide therapy is a well-established treatment to eradicate locally advanced cancer. Several radiopharmaceuticals have been applied to cancer therapy. Chitinase-3-like protein 1 (CHI3L1/YKL40) overexpression is highly correlated with poor outcomes in metastatic ovarian cancer and can be a promising target for targeted therapy. In this study, we report on metronomic CHI3L1-specific antibody radionuclide treatment combined with chemotherapy and evaluate their clinical applications for targeted therapy in metastatic ovarian cancer. Methods: The human ovarian cancer cell line CA5171 was used in vitro and in vivo studies. We investigated the therapeutic response of Lu-177-DTPA-YKL40 antibodies combined with paclitaxel or cisplatin in metastatic CA5171 tumor-bearing mice. We also evaluated the tumor volume, survival, histopathological examinations, and anti-tumor immune responses after treatments. Results: Tumor-bearing mice treated with low-dose Lu-177-DTPA-YKL40 antibodies (200 μCi/twice or 100 μCi/four times a week) and paclitaxel (6 mg/kg) or cisplatin (75 mg/m2) exhibited a dramatic increase in the infiltrated T cell and a significant reduction of tumor size. The combination of the CHI3L1-targeting antibody radionuclide and the chemotherapeutic agents, including paclitaxel and cisplatin, also elicited systematic effects on various subcutaneous, peritoneal-spread, and distant pulmonary metastatic tumors. Lu-177-DTPA-YKL40 antibodies also induce the cell death signal HMGB1 expression in apoptotic tumor cells and stimulate dendritic cell maturation, which results in inducing T cell activation. Conclusion: Combinatory treatment with chemotherapy and low-dose metronomic CHI3L1-specific antibody radionuclide treatment can enhance the anti-tumor effects on local and distant metastatic ovarian cancer. Tumor-specific antibody radionuclide combined with chemotherapy is a potential clinical new strategy for advanced cancer treatment. Citation Format: Chun-Tang Chen, Ming-Cheng Chang, Ping-Fang Chiang, Cheng-Liang Peng, Ying-Cheng Chiang. Synergistic Anti-Tumor Effects of Metastatic Ovarian Cancer on Combinatory Treatment with Chemotherapy and Metronomic CHI3L1-Specific Antibody Radionuclide [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl):Abstract nr P28.