Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Role of EVs in Cancer Development
2.1. Modulation of Antitumor Immunity by Dendritic Cells (DCs)-Derived Extracellular Vesicles (EVs)
2.1.1. DCs-Derived EVs (DEVs)
2.1.2. DEVs Function
2.1.3. Influence of the Adaptive Response
2.2. Modulation of the Immune Response by Tumor-Derived EVs
2.2.1. Tumor-Derived EVs (TDEVs)
2.2.2. TDEVs Function on Myeloid Cells
2.2.3. TDEVs Function on DCs
2.2.4. TDEVs Function on Other Immune Cells
3. DEV-Based Cancer Therapeutics
3.1. DEV-Based Vaccines
3.1.1. DEVs as Tumor Vaccines
3.1.2. DEVs as Vaccines for Oncogenic Pathogens
3.2. DEV-Based Immunotherapies
3.3. Clinical Trials Using DEVs
3.4. The Future of DEVs in Vaccination Approaches
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Targeted Tumor Type | Phase of Trial | n1 | Treatment | Loaded Antigen | Immune Effects | Clinical Outcome | Ref. |
---|---|---|---|---|---|---|---|
NSCLC (stage IIIb and IV) | I | 13 (9) | DEVs from moDC | MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides + CMV and tetanus toxoid peptide (direct or indirect loading) | DTH reactivity against MAGE peptides in 3/9. MAGE-specific T cell responses in 1/3. NK lytic activity in 2/4. CMV responses. Increase of Tregs in 2/3. | Well tolerated. Mild adverse events. Stabilization after progression in 2/9. | [163] |
Melanoma (stage IIIb and IV) | I | 15 | DEVs from moDC | MAGE3168–176 and MAGE3247–258 | Specific T cell responses in peripheral blood not detected. One case of tumor infiltration of activated T cells. NK cell number and NKG2D function recovered in 7/14. NKG2D expression in CD8+ T cells in 6/14. | No toxicity (mild adverse events). One patient exhibited a partial response. | [41,164] |
Colorectal cancer (stage III or IV) | I | 40 | AEVs + GM-CSF | Contain CEA | DTH response as well as a CEA-specific CTL cell response | Well tolerated. Stabilization in 1 and minor response in 1. | [165] |
NSCLC (stage IIIb and IV) | II | 26 (22) | DEVs from IFNγ-matured moDC | MAGE-A1, MAGE-A3, NY-ESO-1, Melan-A/MART1, MAGE-A3-DP04 and EBV peptides. | Tumor antigen-specific T cell responses only in 2/8. Increased NKp30-dependent NK cell functions. | Stabilization with continuation of injections in 7. Long-term stabilization in 1. Hepatotoxicity in 1. | [166] |
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Fernández-Delgado, I.; Calzada-Fraile, D.; Sánchez-Madrid, F. Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines. Cancers 2020, 12, 3558. https://doi.org/10.3390/cancers12123558
Fernández-Delgado I, Calzada-Fraile D, Sánchez-Madrid F. Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines. Cancers. 2020; 12(12):3558. https://doi.org/10.3390/cancers12123558
Chicago/Turabian StyleFernández-Delgado, Irene, Diego Calzada-Fraile, and Francisco Sánchez-Madrid. 2020. "Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines" Cancers 12, no. 12: 3558. https://doi.org/10.3390/cancers12123558
APA StyleFernández-Delgado, I., Calzada-Fraile, D., & Sánchez-Madrid, F. (2020). Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines. Cancers, 12(12), 3558. https://doi.org/10.3390/cancers12123558