TY - JOUR
T1 - Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1
AU - Grabowska, Joanna
AU - Stolk, Dorian A
AU - Nijen Twilhaar, Maarten K
AU - Ambrosini, Martino
AU - Storm, Gert
AU - van der Vliet, Hans J
AU - de Gruijl, Tanja D
AU - van Kooyk, Yvette
AU - den Haan, Joke M M
N1 - Funding Information: Funding: This work was supported by the Dutch Cancer Society (KWF) VU2014-7200 (Y.v.K., T.D.d.G., H.J.v.d.V.) and by grants from NWO ZonMW (TOP 91218024) to J.M.M.d.H. and G.S., from the Phospholipid Research Center to J.M.M.d.H. and Y.v.K., and KWF (VU2016-10449) to J.M.M.d.H., T.D.d.G. and Y.v.K. Funding Information: This work was supported by the Dutch Cancer Society (KWF) VU2014-7200 (Y.v.K., T.D.d.G., H.J.v.d.V.) and by grants from NWO ZonMW (TOP 91218024) to J.M.M.d.H. and G.S., from the Phospholipid Research Center to J.M.M.d.H. and Y.v.K., and KWF (VU2016-10449) to J.M.M.d.H., T.D.d.G. and Y.v.K. The authors would like to thank the U.S. National Institutes of Health (NIH) tetramer core facility for provision of mouse CD1d-PBS57 tetramer for specific NKT detection in FACS analysis. Additionally, the authors are grateful for support of the O|2 Flow Cytometry, GlycO2peptide, MO2Ab and UPC facilities of Amsterdam UMC, location VUmc. We also thank Lucas Czentner for preparation of the liposomes. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/16
Y1 - 2021/1/16
N2 - Successful anti-cancer vaccines aim to prime and reinvigorate cytotoxic T cells and should therefore comprise a potent antigen and adjuvant. Antigen targeting to splenic CD169+ macrophages was shown to induce robust CD8+ T cell responses via antigen transfer to cDC1. Interestingly, CD169+ macrophages can also activate type I natural killer T-cells (NKT). NKT activation via ligands such as α-galactosylceramide (αGC) serve as natural adjuvants through dendritic cell activation. Here, we incorporated ganglioside GM3 and αGC in ovalbumin (OVA) protein-containing liposomes to achieve both CD169+ targeting and superior DC activation. The systemic delivery of GM3-αGC-OVA liposomes resulted in specific uptake by splenic CD169+ macrophages, stimulated strong IFNγ production by NKT and NK cells and coincided with the maturation of cDC1 and significant IL-12 production. Strikingly, superior induction of OVA-specific CD8+ T cells was detected after immunization with GM3-αGC-OVA liposomes. CD8+ T cell activation, but not B cell activation, was dependent on CD169+ macrophages and cDC1, while activation of NKT and NK cells were partially mediated by cDC1. In summary, GM3-αGC antigen-containing liposomes are a potent vaccination platform that promotes the interaction between different immune cell populations, resulting in strong adaptive immunity and therefore emerge as a promising anti-cancer vaccination strategy.
AB - Successful anti-cancer vaccines aim to prime and reinvigorate cytotoxic T cells and should therefore comprise a potent antigen and adjuvant. Antigen targeting to splenic CD169+ macrophages was shown to induce robust CD8+ T cell responses via antigen transfer to cDC1. Interestingly, CD169+ macrophages can also activate type I natural killer T-cells (NKT). NKT activation via ligands such as α-galactosylceramide (αGC) serve as natural adjuvants through dendritic cell activation. Here, we incorporated ganglioside GM3 and αGC in ovalbumin (OVA) protein-containing liposomes to achieve both CD169+ targeting and superior DC activation. The systemic delivery of GM3-αGC-OVA liposomes resulted in specific uptake by splenic CD169+ macrophages, stimulated strong IFNγ production by NKT and NK cells and coincided with the maturation of cDC1 and significant IL-12 production. Strikingly, superior induction of OVA-specific CD8+ T cells was detected after immunization with GM3-αGC-OVA liposomes. CD8+ T cell activation, but not B cell activation, was dependent on CD169+ macrophages and cDC1, while activation of NKT and NK cells were partially mediated by cDC1. In summary, GM3-αGC antigen-containing liposomes are a potent vaccination platform that promotes the interaction between different immune cell populations, resulting in strong adaptive immunity and therefore emerge as a promising anti-cancer vaccination strategy.
KW - Alpha galactosylceramide
KW - Anti-tumor
KW - CD169 macrophage
KW - CDC1
KW - Ganglioside GM3
KW - Invariant natural killer T cell
KW - Liposomes
KW - Vaccination
UR - http://www.scopus.com/inward/record.url?scp=85099928552&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/vaccines9010056
DO - https://doi.org/10.3390/vaccines9010056
M3 - Article
C2 - 33467048
SN - 2076-393X
VL - 9
SP - 1
EP - 19
JO - Vaccines
JF - Vaccines
IS - 1
M1 - 56
ER -