1. Vaccination with DC-SIGN-Targeting αGC Liposomes Leads to Tumor Control, Irrespective of Suboptimally Activated T-Cells.
- Author
-
de Haas, Aram M., Stolk, Dorian A., Schetters, Sjoerd T. T., Goossens-Kruijssen, Laura, Keuning, Eelco, Ambrosini, Martino, Boon, Louis, Kalay, Hakan, Storm, Gert, van der Vliet, Hans J., de Gruijl, Tanja D., and van Kooyk, Yvette
- Subjects
T cells ,PEPTIDOMIMETICS ,CANCER vaccines ,KILLER cells ,VACCINATION - Abstract
Cancer vaccines have emerged as a potent strategy to improve cancer immunity, with or without the combination of checkpoint blockade. In our investigation, liposomal formulations containing synthetic long peptides and α-Galactosylceramide, along with a DC-SIGN-targeting ligand, Lewis Y (Le
Y ), were studied for their anti-tumor potential. The formulated liposomes boosted with anti-CD40 adjuvant demonstrated robust invariant natural killer (iNKT), CD4+ , and CD8+ T-cell activation in vivo. The incorporation of LeY facilitated the targeting of antigen-presenting cells expressing DC-SIGN in vitro and in vivo. Surprisingly, mice vaccinated with LeY -modified liposomes exhibited comparable tumor reduction and survival rates to those treated with untargeted counterparts despite a decrease in antigen-specific CD8+ T-cell responses. These results suggest that impaired induction of antigen-specific CD8+ T-cells via DC-SIGN targeting does not compromise anti-tumor potential, hinting at alternative immune activation routes beyond CD8+ T-cell activation. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF