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

Publication date: Dec 05, 2023

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.

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Concepts Keywords
Agonists Chemical
B16f10 Conjugation
Chemistry Evs
Efficient Extracellular
Vaccines Free
Metabolic
Modulate
Survival
Tagging
Tags
Tumor
Universal
Vaccines
Vesicles

Semantics

Type Source Name
disease MESH cancer
disease MESH lymphoma
disease MESH melanoma
pathway KEGG Melanoma
drug DRUGBANK Coenzyme M
drug DRUGBANK Cycloserine
pathway KEGG Endocytosis
disease MESH glioblastoma
drug DRUGBANK Tretamine
drug DRUGBANK Biotin
drug DRUGBANK Methylergometrine
drug DRUGBANK Lysergic acid diethylamide

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