Glycan-modified liposomes boost CD4+ and CD8+ T-cell responses by targeting DC-SIGN on dendritic cells

Wendy W.J. Unger* (Corresponding Author), Astrid J. van Beelen, Sven C. Bruijns, Medha Joshi, Cynthia M. Fehres, Louis van Bloois, Marleen I. Verstege, Martino Ambrosini, Hakan Kalay, Kamran Nazmi, Jan G. Bolscher, Erik Hooijberg, Tanja D. de Gruijl, Gert Storm, Yvette van Kooyk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

99 Citations (Scopus)

Abstract

Cancer immunotherapy requires potent tumor-specific CD8+ and CD4+ T-cell responses, initiated by dendritic cells (DCs). Tumor antigens can be specifically targeted to DCs in vivo by exploiting their expression of C-type lectin receptors (CLR), which bind carbohydrate structures on antigens, resulting in internalization and antigen presentation to T-cells. We explored the potential of glycan-modified liposomes to target antigens to DCs to boost murine and human T-cell responses. Since DC-SIGN is a CLR expressed on DCs, liposomes were modified with DC-SIGN-binding glycans Lewis (Le)B or LeX. Glycan modification of liposomes resulted in increased binding and internalization by BMDCs expressing human DC-SIGN. In the presence of LPS, this led to 100-fold more efficient presentation of the encapsulated antigens to CD4+ and CD8+ T-cells compared to unmodified liposomes or soluble antigen. Similarly, incubation of human moDC with melanoma antigen MART-1-encapsulated liposomes coated with LeX in the presence of LPS led to enhanced antigen-presentation to MART-1-specific CD8+ T-cell clones. Moreover, this formulation drove primary CD8+ T-cells to differentiate into high numbers of tetramer-specific, IFN-γ-producing effector T-cells. Together, our data demonstrate the potency of a glycoliposome-based vaccine targeting DC-SIGN for CD4 + and CD8+ effector T-cell activation. This approach may offer improved options for treatment of cancer patients and opens the way to in situ DC-targeted vaccination.

Original languageEnglish
Pages (from-to)88-95
Number of pages8
JournalJournal of controlled release
Volume160
Issue number1
DOIs
Publication statusPublished - 30 May 2012
Externally publishedYes

Keywords

  • Anti-tumor immunity
  • Antigen-targeting
  • CD4 T-cells
  • CD8 T-cells
  • DC-SIGN
  • Glycans

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