Efficient production of extracellular vesicles for enhanced cancer immunotherapy
image: Extracellular vesicles serve as essential mediators of communication between immune cells and tumor cells, and the recent advances in artificial induction strategies offer an adaptable and efficient platform for engineering extracellular vesicles, enabling their application as next-generation strategies in cancer immunotherapy.
Credit: Nano Research, Tsinghua University Press
Extracellular vesicles (EVs) are membrane-bound particles secreted by cells that carry donor cell-derived proteins, nucleic acids, lipids, and metabolites, playing crucial regulatory roles in cellular communication. Their biological functions are intrinsically linked to the nature of the donor cell. For instance, immune cell-derived EVs activate and recruit cytotoxic T lymphocytes by providing major histocompatibility complex (MHC), co-stimulatory signals, inflammatory factors, and chemokines, thereby inducing tumor cell apoptosis. Conversely, tumor cell-derived EVs contain tumor-associated antigens (TAAs) and double-stranded DNA, acting as a "natural antigen library" to stimulate efficient maturation of dendritic cells (DCs) and enhance their antigen processing and presentation capabilities. Consequently, EVs show vast application potential in areas like immune regulation, cancer vaccines, drug formulations, and disease diagnostics.
However, under standard culture conditions, cells secrete only about 50 EVs per minute. This low yield presents significant challenges for scaling up production and ensuring quality control in EV-based therapies. Traditional methods, such as sonication, mechanical extrusion, and freeze-thaw cycles, lack precise control over the applied physical forces, often compromising the bioactivity and integrity of the produced EVs.
This review focuses on recently developed artificial EV induction strategies, including radiation, pharmacological agents, cellular dehydration, and mechanically stimulated microfluidic chips. It details their respective advantages for generating tumor neoantigens, developing personalized tumor vaccines, reducing safety risks, and achieving active drug loading. Compared to conventional EV production methods, these novel artificial induction techniques significantly boost EV yield while simultaneously enhancing their desired immunotherapeutic activity. Furthermore, the review provides workflow recommendations for the clinical translation of these methods, covering aspects of culture, purification, and preservation. Finally, the article outlines future directions for artificial EV induction technology, including integration with genetic engineering, chemical modification, and physical adsorption approaches. Following validation of clinical safety and efficacy, artificially induced EV technology holds promise as a next-generation bioengineerable platform for tumor immunotherapy.
The review was authored by Xiaolong Wang, a second-year Master's student, under the supervision of Prof. Jianxun Ding at the State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences (CIAC, CAS).
This work was supported financially by the National Natural Science Foundation of China (Nos. U23A20591, 52273158, 52273159, and W2421115), the Science and Technology Department Project of Jilin Province (No. 20240101002JJ), and the Youth Innovation Promotion Association of Chinese Academy of Sciences (No. Y2023066).
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.