Large-Scale Production and Therapeutic Evaluation of Exosomes for Cancer Treatment.

introductionLung cancer remains one of the most prevalent and deadly malignancies worldwide, representing a major global health challenge. According to the latest global cancer statistics, lung cancer accounts for approximately 11.6% of all new cancer diagnoses and 19.8% of cancer-related deaths, making it the leading cause of cancer mortality. MATERIAL AND

methodsIn the present study, THP-1 cells, a well-established human pro-monocytic cell line, were selected for exosome production due to their immune-regulatory potential and capacity to secrete vesicles rich in functional proteins and cytokines. To ensure the isolation of exosomes exclusively secreted by THP-1 cells, the culture system was adapted to serum-free conditions, eliminating contamination from animal-derived exosomes commonly present in fetal bovine serum.

resultsTHP-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.

conclusionThis study comprises a progress about a scalable bioprocess platform for the efficient production, purification, and functional validation of THP-1-derived exosomes. The optimized stirred-tank bioreactor and cross-flow ultrafiltration system significantly improved exosome yield and purity, enabling the quantities required for preclinical applications. Functionally, the resulting exosomes demonstrated potent antitumor effects in 3D tumor models, supporting their potential use as immunomodulatory nanotherapeutics in oncology. Future research should focus on optimizing cargo loading strategies,