MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses

M.A. Boks, Martino Ambrosini, Sven C.M. Bruijns, Hakan Kalay, Louis van Bloois, Gerrit Storm, Juan J. Garcia-Vallejo, Y. van Kooyk

Research output: Contribution to journalArticleAcademicpeer-review

36 Citations (Scopus)

Abstract

Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with strong adjuvants such as TLR ligands. However, often these adjuvants have off-target effects, and would benefit from a DC-specific targeting strategy, similar to the tumour antigen. The goal of this study was to develop a strategy for specifically targeting DC with tumour antigen and adjuvant by using glycoliposomes. We have generated liposomes containing the glycan Lewis(Le)X which is highly specific for the C-type lectin receptor DC-SIGN expressed by DC. LeX-modified liposomes were taken up by human monocyte-derived DC in a DC-SIGN-specific manner. As adjuvants we incorporated the TLR ligands Pam3CySK4, Poly I:C, MPLA and R848 into liposomes and compared their adjuvant capacity on DC. Incorporation of the TLR4 ligand MPLA into glycoliposomes induced DC maturation and production of pro-inflammatory cytokines, in a DC-SIGN-specific manner, and DC activation was comparable to administration of soluble MPLA. Incorporation of MPLA into glycoliposomes significantly enhanced antigen cross-presentation of the melanoma tumour antigen gp100280–288 peptide to CD8+ T cells compared to non-glycosylated MPLA liposomes. Importantly, antigen cross-presentation of the gp100280–288 peptide was significantly higher using MPLA glycoliposomes compared to the co-administration of soluble MPLA with glycoliposomes. Taken together, our data demonstrates that specific targeting of a gp100 tumour antigen and the adjuvant MPLA to DC-SIGN-expressing DC enhances the uptake of peptide-containing liposomes, the activation of DC, and induces tumour antigen-specific CD8+ T cell responses. These data demonstrate that adjuvant-containing glycoliposome-based vaccines
Original languageUndefined
Pages (from-to)37-46
JournalJournal of controlled release
Volume216
DOIs
Publication statusPublished - 2015

Keywords

  • METIS-315209
  • IR-99934

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