Abstract 6381: Extracellular vesicle-mediated co-delivery of FSL-1 and LY2157299 for immunotherapy of small-cell lung cancer liver metastases.

Abstract Small-cell lung cancer (SCLC) frequently metastasizes to the liver, where macrophage-dominated immunosuppression sustains tumor outgrowth. Bioinformatic analyses of SCLC liver metastases implicate macrophage metabolism as a driver of hepatic progression. We engineered extracellular vesicles (EVs) co-delivering FSL-1 (TLR2/6 agonist) and LY2157299/galunisertib (TGF-βRI inhibitor) to reprogram macrophages. In vitro, dual-loaded EVs more efficiently shifted macrophages toward pro-inflammatory, antigen-presenting states. In vivo, EVs efficiently targeted intrahepatic tumor sites, decreased liver tumor growth, and prolonged mouse survival. These data support EV-mediated co-delivery of FSL-1 and LY2157299 as a macrophage-centric strategy for SCLC liver metastasis. Citation Format: Yue Huang, Amira Kazi, Rajesh Kumar, Kanak Parmar, Chiori Tabe, Ajit Kumar Sharma, Anish Thomas, . Extracellular vesicle-mediated co-delivery of FSL-1 and LY2157299 for immunotherapy of small-cell lung cancer liver metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6381.