This simple, straightforward, and scalable production of dendritic cell-derived extracellular vesicles (DC-EVs) employs low-power, near-UV light. Dendritic cells are the most potent antigen-presenting cells and the key initiator of a tumor-specific immune response. For these reasons, dendritic cell therapy and dendritic cell-based vaccines have emerged as candidates for cancer immunotherapies. However, dendritic cells are unstable, difficult to store for long periods and require strict quality control. Therefore, implementing dendritic cell therapy across large populations is costly. In contrast to dendritic cells, the secreted extracellular vesicles (DC-EVs) possess properties that overcome these drawbacks while maintaining immune-modulation properties, making them a more suitable immunotherapeutic candidate. However, traditional methods of induction, production, and purification of dendritic cell-derived extracellular vesicles (DC-Evs) aren’t efficient.
Researchers at the University of Florida have discovered the use of low-power, near-UV light to induce the production of immune-competent extracellular vesicles from dendritic cells. Compared to other traditional physical stimulations, light induction is simple, scalable, and requires no specific equipment setup. The resulting extracellular vesicles are consistent with native ones, demonstrated by in vivo biodistribution, immunogenicity, and administration safety properties in a mouse model indicating they are safe and have a high potential for translating to human uses.
Phototherapy-based stimulation of dendritic cells for simple and scalable production of extracellular vesicles used in immunotherapy and immune-modulation strategies
Using low-power, near-UV light to induce the production of immune-competent dendritic cellular-extracellular vesicles leads to a 5-15-fold enhancement in the production rate, while maintaining quality and immune function in the resulting vesicles. Stimulation of dendritic cells using phototherapy enables scalable production of the vesicles in cell culture incubators or bioreactors on demand at the manufacturing scale, without the requirement of a specific equipment setup. The resulting extracellular vesicles exhibit size, zeta potential, morphology, immune surface markers and cytokines, biocompatibility, cellular uptake behavior, and immune-modulatory ability consistent with native vesicles from dendritic cells produced in the absence of phototherapy-based stimulation. Additionally, they present biodistribution, immunogenicity, and administration safety properties in mouse models, indicating suitability for use in humans. These extracellular vesicles can modulate immune reactions on their own in immunotherapeutic strategies, or they can serve as delivery agents for different cargo molecules including drugs, specific tissue targeting molecules, immunotherapeutic agents, or antigens suitable for vaccines.
