Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines

• Published in: Nature communications Vol. 14; no. 1; p. 8047
• Main Authors: Bhatta, Rimsha, Han, Joonsu, Liu, Yusheng, Bo, Yang, Lee, David, Zhou, Jiadiao, Wang, Yueji, Nelson, Erik Russell, Chen, Qian, Zhang, Xiaojia Shelly, Hassaneen, Wael, Wang, Hua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.12.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 14/1; 14/19; 14/34; 631/250/251/1567; 631/61/350/354; 631/67/1059/2325; 631/67/1059/4042; 639/166/985; Antitumor activity; Cancer; Cancer vaccines; Cancer Vaccines - metabolism; CD8 antigen; Cell activation; Cell Communication; Cell interactions; Cellular communication; Chemical synthesis; Conjugation; Dendritic cells; Extracellular vesicles; Extracellular Vesicles - metabolism; Humanities and Social Sciences; Humans; Lymphocytes; Lymphocytes T; Lymphoma; Melanoma; Metabolism; multidisciplinary; Science; Science (multidisciplinary); Skin Neoplasms - metabolism; Survival; Tags; Therapeutic applications; Toll-like receptors; Tumors; Vaccines; Vesicles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43914-8

As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs and modulate the interaction between EVs and recipient cells are still lacking. Here we report a facile and universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface chemical tags enable conjugation of molecules via efficient click chemistry, for the tracking and targeted modulation of EVs. In the context of tumor EV vaccines, we show that the conjugation of toll-like receptor 9 agonists onto EVs enables timely activation of dendritic cells and generation of superior antitumor CD8 + T cell response. These lead to 80% tumor-free survival against E.G7 lymphoma and 33% tumor-free survival against B16F10 melanoma. Our study yields a universal technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV vaccines. Extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. Here, the authors report a universal metabolic tagging technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV-based cancer vaccines.