Ilgın Kımız Geboloğlu, Suphi Ş. Öncel
INTRODUCTION: Addressing these limitations will be a crucial step toward realizing the full potential of exosome-based nanomedicine as a next-generation therapeutic strategy in the treatment of lung cancer and other malignancies. MATERIAL AND METHODS: Subsequently, cells were produced in a stirred-tank bioreactor, and a cross-flow ultrafiltration system was optimized for isolation, creating a bioprocess system for large-scale production of exosomes. The isolated exosomes were characterized for size distribution, morphology, homogeneity, concentration, protein content, and surface markers. Finally, after loading the cargo molecule into exosomes, their therapeutic efficacy was further evaluated in a three-dimensional carcinoma spheroid model (Figure 1). RESULTS: THP-1 cells successfully adapted to serum-free culture conditions and produced exosomes efficiently in a stirred-tank bioreactor. The optimized ultrafiltration system achieved high recovery rates and excellent exosome purity, as validated by nanoparticle tracking analysis, scanning transmission electron microscopy, and immunoblotting for characteristic exosomal markers. The improved bioprocess significantly increased exosome yield, thereby overcoming one of the major bottlenecks in their clinical scalability. Functionally, the application of loaded THP-1-derived exosomes to carcinoma spheroids led to a notable reduction in spheroid size and cell viability, demonstrating their potential tumor-suppressive and antigen-delivery capabilities. These findings highlight the immunostimulatory potential of immune cell-derived exosomes, which may act through pathways involving antigen presentation and modulation of immune signaling cascades. The scalability of this bioprocess, combined with the therapeutic efficacy of THP-1-derived exosomes, emphasize their promise as next-generation immunotherapeutic platforms for cancer treatment. CONCLUSION: biodistribution analysis, and optimization of targeting strategies for specific tumor types, including lung cancer. Ultimately, integrating scalable manufacturing with precise therapeutic design will accelerate the clinical translation of immune cell-derived exosomes as safe and effective platforms in cancer nanomedicine.