(346e) Facile, Scalable Dendritic Cell-Derived Extracellular Blebs for a Cancer Vaccine

Authors: 
Thone, M., UC Irvine
Ingato, D., UC Irvine
Dixit, A., UC Irvine
Kwon, Y. J., UC Irvine
Immunotherapy activates the body’s own immune system to fight disease. This is commonly accomplished by the use of vaccines, which are capable of evoking T cell immune responses against specific antigens, allowing for targeted toxicity effects. In particular, dendritic cells (DCs) have been thoroughly investigated for use in vaccines as they are professional antigen presenters and have proven to facilitate T cell response in vivo for eradication of tumors. Furthermore, a patients’ own cells could be used to develop the therapy allowing for complete biocompatibility and personalization. While DC-based vaccines are promising, they suffer from inherent risks, poorly defined good manufacturing protocols, and poor storage capability. Instead, particles derived from cells termed extracellular vesicles (EVs) could be a promising alternative to maintain the bio-active properties of cells with fewer risks and a more stable design for transport and storage. DC-derived EVs have demonstrated eradication of tumors similarly or better than DCs generating the possibility for a cell-free cancer vaccine. However, similar to other EV applications, the use and clinical translation of EVs has been limited by low production efficiency and lack of homogeneity, which are critical factors in development of a safe and effective vaccine.

We address these challenges by applying a unique chemically-induced production technique that initiates rapid blebbing of the DC membrane. This process generates high yields of micro-scale extracellular blebs (EBs) that are identical in cellular maturation state and presentation to their parent DCs. Both in vitro and in vivo, EBs from mature DCs induced potent T cell responses and were successful at preventing tumor growth in a tumor challenge. This technique presents a scalable option for producing safe cell-free vaccines that could meet commercial standardization requirements.