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Updated: Jan 20, 2026
In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination
Sophie K Horrevorts1, Dorian A Stolk1, Rieneke van de Ven2,3
1Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Abstract:
Tumors that lack T cell infiltration are less likely to respond to immune checkpoint inhibition and could benefit from cancer vaccination for the initiation of anti-tumor T cell responses. An attractive vaccine strategy is in vivo targeting of dendritic cells (DCs), key initiators of antigen-specific T cell responses. In this study we generated tumor-derived apoptotic extracellular vesicles (ApoEVs), which are potentially an abundant source of tumor-specific neo-antigens and other tumor-associated antigens (TAAs), and which can be manipulated to express DC-targeting ligands for efficient antigen delivery. Our data demonstrates that by specifically modifying the glycocalyx of tumor cells, high-mannose glycans can be expressed on their cell surface and on extracellular vesicles derived after the induction of apoptosis. High-mannose glycans are the natural ligands of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a dendritic cell associated C-type lectin receptor (CLR), which has the ability to efficiently internalize its cargo and direct it to both major histocompatibility complex (MHC)-I and MHC-II pathways for the induction of CD8+ and CD4+ T cell responses, respectively. Compared to unmodified ApoEVs, ApoEVs carrying DC-SIGN ligands are internalized to a higher extent, resulting in enhanced priming of tumor-specific CD8+ T cells. This approach thus presents a promising vaccination strategy in support of T cell-based immunotherapy of cancer.
Insights
Engineered extracellular vesicles carrying tumor antigens can enhance anti-tumor T cell responses. This cancer vaccination strategy targets dendritic cells (DCs) for improved T cell priming, offering a promising approach for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Tumors lacking T cell infiltration resist immune checkpoint inhibition.
- Cancer vaccination is crucial for initiating anti-tumor T cell responses.
- Dendritic cells (DCs) are key initiators of antigen-specific T cell responses.
Purpose of the Study:
- To develop a novel cancer vaccination strategy using tumor-derived apoptotic extracellular vesicles (ApoEVs).
- To engineer ApoEVs to target DCs for efficient antigen delivery and T cell priming.
- To evaluate the efficacy of modified ApoEVs in stimulating anti-tumor T cell immunity.
Main Methods:
- Generation of tumor-derived apoptotic extracellular vesicles (ApoEVs).
- Modification of tumor cell glycocalyx to express high-mannose glycans on ApoEVs.
- Utilizing the high-mannose glycan interaction with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) for enhanced uptake.
- Assessing T cell responses, including CD8+ and CD4+ T cell priming, via MHC-I and MHC-II pathways.
Main Results:
- Engineered ApoEVs successfully expressed high-mannose glycans, acting as ligands for DC-SIGN.
- DC-SIGN-targeted ApoEVs demonstrated significantly higher internalization by DCs compared to unmodified ApoEVs.
- Enhanced priming of tumor-specific CD8+ T cells was observed with modified ApoEVs.
- This approach facilitates antigen presentation through both MHC-I and MHC-II pathways.
Conclusions:
- Modified ApoEVs represent a potent vaccine strategy for cancer immunotherapy.
- Targeting DCs via DC-SIGN with engineered ApoEVs enhances anti-tumor T cell responses.
- This approach holds promise for overcoming resistance to current immunotherapies in T cell-poor tumors.
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04:05Immunocapture and Flow Cytometry of Extracellular Vesicles for Antigenic Characterization
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