In situ delivery of tumor antigen- and adjuvant-loaded liposomes boosts antigen-apecific T-Cell responses by human dermal dendritic cells

M.A. Boks, Sven C.M. Bruijns, Martino Ambrosini, Hakan Kalay, Louis van Bloois, Gerrit Storm, T.D. de Gruijl, Y. van Kooyk

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Abstract

Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor antigen with an adjuvant is beneficial for cross-presentation and the induction of tumor-specific T-cell responses. We therefore developed liposomes that contain the melanoma-associated antigen glycoprotein 100280-288 peptide and Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) as adjuvant. These liposomes are efficiently taken up by monocyte-derived DCs, and antigen presentation to CD8+ T cells was significantly higher with MPLA-modified liposomes as compared with non-modified liposomes or the co-administration of soluble MPLA. We used a human skin explant model to evaluate the efficiency of intradermal delivery of liposomes. Liposomes were efficiently taken up by CD1a+ and especially CD14+ dermal DCs. Induction of CD8+ T–cell responses by emigrated dermal DCs was significantly higher when MPLA was incorporated into the liposomes as compared with non-modified liposomes or co-administration of soluble MPLA. Thus, the modification of antigen-carrying liposomes with TLR ligand MPLA significantly enhances tumor-specific T-cell responses by dermal DCs and is an attractive vaccination strategy in human skin
Original languageEnglish
Pages (from-to)2697-2704
JournalJournal of investigative dermatology
Volume135
Issue number11
DOIs
Publication statusPublished - 2015

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T-cells
Langerhans Cells
Neoplasm Antigens
Liposomes
T-Lymphocytes
Antigens
Tumors
Dendritic Cells
Skin
Neoplasms
Vaccination
Cross-Priming
Melanoma-Specific Antigens
Ligands
Toll-Like Receptor 4
Antigen Presentation
Immunotherapy
monophosphoryl lipid A
Monocytes
Glycoproteins

Cite this

Boks, M.A. ; Bruijns, Sven C.M. ; Ambrosini, Martino ; Kalay, Hakan ; van Bloois, Louis ; Storm, Gerrit ; de Gruijl, T.D. ; van Kooyk, Y. / In situ delivery of tumor antigen- and adjuvant-loaded liposomes boosts antigen-apecific T-Cell responses by human dermal dendritic cells. In: Journal of investigative dermatology. 2015 ; Vol. 135, No. 11. pp. 2697-2704.
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title = "In situ delivery of tumor antigen- and adjuvant-loaded liposomes boosts antigen-apecific T-Cell responses by human dermal dendritic cells",
abstract = "Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor antigen with an adjuvant is beneficial for cross-presentation and the induction of tumor-specific T-cell responses. We therefore developed liposomes that contain the melanoma-associated antigen glycoprotein 100280-288 peptide and Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) as adjuvant. These liposomes are efficiently taken up by monocyte-derived DCs, and antigen presentation to CD8+ T cells was significantly higher with MPLA-modified liposomes as compared with non-modified liposomes or the co-administration of soluble MPLA. We used a human skin explant model to evaluate the efficiency of intradermal delivery of liposomes. Liposomes were efficiently taken up by CD1a+ and especially CD14+ dermal DCs. Induction of CD8+ T–cell responses by emigrated dermal DCs was significantly higher when MPLA was incorporated into the liposomes as compared with non-modified liposomes or co-administration of soluble MPLA. Thus, the modification of antigen-carrying liposomes with TLR ligand MPLA significantly enhances tumor-specific T-cell responses by dermal DCs and is an attractive vaccination strategy in human skin",
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In situ delivery of tumor antigen- and adjuvant-loaded liposomes boosts antigen-apecific T-Cell responses by human dermal dendritic cells. / Boks, M.A.; Bruijns, Sven C.M.; Ambrosini, Martino; Kalay, Hakan; van Bloois, Louis; Storm, Gerrit; de Gruijl, T.D.; van Kooyk, Y.

In: Journal of investigative dermatology, Vol. 135, No. 11, 2015, p. 2697-2704.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - In situ delivery of tumor antigen- and adjuvant-loaded liposomes boosts antigen-apecific T-Cell responses by human dermal dendritic cells

AU - Boks, M.A.

AU - Bruijns, Sven C.M.

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AU - van Bloois, Louis

AU - Storm, Gerrit

AU - de Gruijl, T.D.

AU - van Kooyk, Y.

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AB - Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor antigen with an adjuvant is beneficial for cross-presentation and the induction of tumor-specific T-cell responses. We therefore developed liposomes that contain the melanoma-associated antigen glycoprotein 100280-288 peptide and Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) as adjuvant. These liposomes are efficiently taken up by monocyte-derived DCs, and antigen presentation to CD8+ T cells was significantly higher with MPLA-modified liposomes as compared with non-modified liposomes or the co-administration of soluble MPLA. We used a human skin explant model to evaluate the efficiency of intradermal delivery of liposomes. Liposomes were efficiently taken up by CD1a+ and especially CD14+ dermal DCs. Induction of CD8+ T–cell responses by emigrated dermal DCs was significantly higher when MPLA was incorporated into the liposomes as compared with non-modified liposomes or co-administration of soluble MPLA. Thus, the modification of antigen-carrying liposomes with TLR ligand MPLA significantly enhances tumor-specific T-cell responses by dermal DCs and is an attractive vaccination strategy in human skin

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