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Strategies for Small Extracellular Vesicle-Based Cancer Immunotherapy

Chen, Yundi, Tang, Shasha, Cai, Fengfeng, Wan, Yuan·2024·Research
DOI 10.34133/research.0421PMC PMC11260559
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Abstract

Extracellular vesicles (EVs) are lipid bilayer-enclosed vesicles released by cells. EVs encapsulate proteins and nucleic acids of their parental cell and efficiently deliver the cargo to recipient cells. These vesicles act as mediators of intercellular communication and thus play a crucial role in various physiological and pathological processes. Moreover, EVs hold promise for clinical use. They have been explored as drug delivery vehicles, therapeutic agents, and targets for disease diagnosis. In the landscape of cancer research, while strides have been made in EV-focused cancer physiopathology, liquid biopsy, and drug delivery, the exploration of EVs as immunotherapeutic agents may not have seen substantial progress to date. Despite promising findings reported in cell and animal studies, the clinical translation of EV-based cancer immunotherapeutics encounters challenges. Here, we review the existing strategies used in EV-based cancer immunotherapy, aiming to propel the development of this emerging yet crucial field.

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Figure. Existing strategies for sEV-based cancer immunotherapy. (A) TEVs as cancer vaccines directly present/deliver TAAs to APCs. (B) Tumor cell lysate-loaded EVs as cancer vaccines present/deliver TAAs to APCs. (C) TAA-expressing EVs produced from transfected donor cells as cancer vaccines present/deliver TAAs to APCs. (D) EVs as cancer vaccines confer TAAs or neoantigens onto tumor cell surfaces, triggering host immunity specifically against TAA- or neoantigen-expressing cancer cells. (E) EVs and OMVs as nanocarriers deliver adjuvants and/or immunomodulators, boosting immune responses. (F) Anti-PD-L1 ligand-expressing EVs or OMVs as immunotherapeutic agents block PD-L1, achieving immune checkpoint blockade. (G) CAR-T EVs as immunotherapeutic agents deliver GrB and other cytotoxins to tumor cells, inducing tumor apoptosis. (H) EVs as nanocarriers facilitate cytosolic delivery of OVs, enhancing tumor cell lysis. (I) EVs as nanocarriers deliver plasmid-encoding CRISPR-Cas9 and guide RNA (gRNA), enabling endogenous generation of CRISPR-Cas9 complex for gene editing in tumor cells.
Figure. Existing strategies for sEV-based cancer immunotherapy. (A) TEVs as cancer vaccines directly present/deliver TAAs to APCs. (B) Tumor cell lysate-loaded EVs as cancer vaccines present/deliver TAAs to APCs. (C) TAA-expressing EVs produced from transfected donor cells as cancer vaccines present/deliver TAAs to APCs. (D) EVs as cancer vaccines confer TAAs or neoantigens onto tumor cell surfaces, triggering host immunity specifically against TAA- or neoantigen-expressing cancer cells. (E) EVs and OMVs as nanocarriers deliver adjuvants and/or immunomodulators, boosting immune responses. (F) Anti-PD-L1 ligand-expressing EVs or OMVs as immunotherapeutic agents block PD-L1, achieving immune checkpoint blockade. (G) CAR-T EVs as immunotherapeutic agents deliver GrB and other cytotoxins to tumor cells, inducing tumor apoptosis. (H) EVs as nanocarriers facilitate cytosolic delivery of OVs, enhancing tumor cell lysis. (I) EVs as nanocarriers deliver plasmid-encoding CRISPR-Cas9 and guide RNA (gRNA), enabling endogenous generation of CRISPR-Cas9 complex for gene editing in tumor cells.CC BY · PubMed Central

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Metadata

Authors
Chen, Y., Tang, S., Cai, F., & Wan, Y.
Venue
Research
Publisher
American Association for the Advancement of Science (AAAS)
Published
2024-01
Volume
7
ISSN
2639-5274
DOI
10.34133/research.0421
PMC
PMC11260559
Cited by
26
References
5
Language
en

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CoChat. (2026). Citation check: Strategies for Small Extracellular Vesicle-Based Cancer Immunotherapy. https://app.cochat.ai/papers/10.34133/research.0421
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Chen, Y., Tang, S., Cai, F., & Wan, Y. (2024). Strategies for Small Extracellular Vesicle-Based Cancer Immunotherapy. Research. https://doi.org/10.34133/research.0421