FAP-based Targeted Radionuclides as Immune Modulators in Ovarian and Breast Cancer

Targeted radionuclide therapy (TRT) is emerging as a transformative approach in oncology, offering both cytotoxic and immunomodulatory effects within the tumor microenvironment (TME). This project explores FAP-targeted TRT as a strategy to overcome immune resistance in ovarian cancer (OC) and triple-negative breast cancer (TNBC), two aggressive, treatment-resistant cancers with high unmet clinical needs. By directing ionizing radiation to FAP-expressing cancer-associated fibroblasts, TRT aims to disrupt the immunosuppressive TME and enhance immune infiltration. The research will investigate the therapeutic synergy between FAP-based TRT and immune checkpoint inhibitors (ICIs), focusing on β-emitters (177Lu, 161Tb) and α-emitters (225Ac). Through preclinical studies in syngeneic and oncogenic murine models, the project will assess biodistribution, immune activation, and tumor response. Key objectives include characterizing immune modulation, optimizing treatment regimens, and evaluating radiobiological mechanisms. By integrating radiopharmaceutical science, immunotherapy, and translational oncology, this project aims to develop a robust combination therapy platform for OC and TNBC which can help bring it toward clinical application, offering a novel, high-efficacy treatment strategy for aggressive female cancers.