Abstract 6174: Macrophage-based immunotherapy of platinum-resistant ovarian cancer

Abstract Platinum-resistant ovarian cancer remains one of the greatest challenges in oncology, with limited treatment options and poor survival outcomes. To address this unmet need we develop MDC-735, a novel allogeneic, off-the-shelf macrophage-based therapy. MDC-735 leverages the breakthrough TRAIN (TRAnsfer of Iron-binding proteiN) mechanism, discovered by our team, to enable macrophages to deliver drug-loaded ferritin complexes directly to tumor cells. This approach bypasses drug resistance, penetrates hypoxic tumor regions, and overcomes challenges faced by conventional therapies. In preclinical studies, MDC-735 demonstrated remarkable efficacy in multiple solid tumor models, including platinum-resistant ovarian cancer, showing significant tumor shrinkage, long-term animal survival and immune activation. This unique therapy employs allogeneic macrophages loaded with a tubulin polymerization inhibitor, achieving targeted delivery while minimizing systemic toxicity. The ability of MDC-735 to alter the tumor microenvironment and induce immune resistance to recurrence highlights its potential as a game-changing therapy. This innovative therapy promises to transform the landscape of platinum-resistant ovarian cancer treatment, providing a scalable and effective solution for a disease with limited options. Citation Format: Jan Brancewicz, Maciej Bialasek, Bartłomiej Taciak, Ilona Marszalek, Konrad Gabrusiewicz, Tomasz Rygiel, Magdalena Krol. Macrophage-based immunotherapy of platinum-resistant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6174.