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

Boks, Martine A.; Ambrosini, Martino; Bruijns, Sven C. M.; Kalay, Hakan; Bloois, Louis van; Storm, Gert; García-Vallejo, Juan J.; Kooyk, Yvette van

doi:10.1016/j.jconrel.2015.06.033

Cited by 62 publications

(43 citation statements)

References 57 publications

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“…Our results are in line with those reported by Soema et al who show that encapsulation of M1 peptide in virosomes strongly increased the uptake of the peptide by DCs in vitro . Another study demonstrates that loading melanoma tumor antigen gp100 peptide to MPLA‐incorporating glycoliposomes efficiently enhanced the cross‐presentation of peptide to CD8 T cells …”

Section: Discussionsupporting

confidence: 92%

“…A study reported that incorporation of MPLA into virosomes derived from respiratory syncytial virus (RSV) strongly enhanced the ability of the virosomes to activate mouse APCs . Another study reported that incorporation of MPLA into glycoliposomes not only induced DC maturation, but also enhanceds cross‐presentation of liposome‐conjugated tumor antigen to CD8 T cells . Activation of APCs by membrane‐incorporated MPLA induces the expression of co‐stimulatory molecules on the cell surface and increases cytokine release, thereby enabling efficient generation of CD8 T cell immunity.…”

Section: Discussionmentioning

confidence: 99%

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Monophosphoryl Lipid A‐Adjuvanted Virosomes with Ni‐Chelating Lipids for Attachment of Conserved Viral Proteins as Cross‐Protective Influenza Vaccine

Dong

Bhide

Marsman

et al. 2018

Biotechnology Journal

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Induction of CD8 cytotoxic T cells (CTLs) to conserved internal influenza antigens, such as nucleoprotein (NP), is a promising strategy for the development of cross-protective influenza vaccines. However, influenza NP protein alone cannot induce CTL immunity due to its low capacity to activate antigen-presenting cells (APCs) and get access to the MHC class I antigen processing pathway. To facilitate the generation of NP-specific CTL immunity the authors develop a novel influenza vaccine consisting of virosomes with the Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) and the metal-ion-chelating lipid DOGS-NTA-Ni incorporated in the membrane. In vitro, virosomes with incorporated MPLA induce stronger activation of APCs than unadjuvanted virosomes. Virosomes modified with DOGS-NTA-Ni show high conjugation efficacy for his-tagged proteins and facilitate efficient uptake of conjugated proteins by APCs. Immunization of mice with MPLA-adjuvanted virosomes with attached NP results in priming of NP-specific CTLs while MPLA-adjuvanted virosomes with admixed NP are inefficient in priming CTLs. Both vaccines induce equally high titers of NP-specific antibodies. When challenged with heterosubtypic influenza virus, mice immunized with virosomes with attached or admixed NP are protected from severe weight loss. Yet, unexpectedly, they show more weight loss and more severe disease symptoms than mice immunized with MPLA-virosomes without NP. Taken together, these results indicate that virosomes with conjugated antigen and adjuvant incorporated in the membrane are effective in priming of CTLs and eliciting antigen-specific antibody responses in vivo. However, for protection from influenza infection NP-specific immunity appears not to be advantageous.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Monophosphoryl Lipid A‐Adjuvanted Virosomes with Ni‐Chelating Lipids for Attachment of Conserved Viral Proteins as Cross‐Protective Influenza Vaccine

Dong

Bhide

Marsman

et al. 2018

Biotechnology Journal

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“…In this study, we pursued the development of targeted nanoparticles as an antigen delivery platform for LCs to address the limitations of antibody-based approaches. Liposomes represent versatile nanoparticles that have been approved for the delivery of chemotherapeutics in Kaposi's sarcoma and allow for the co-formulation of adjuvants 27,28 . They can be targeted to glycan-binding proteins (GBPs) including CLRs or sialic acidbinding immunoglobulin-like lectins (Siglecs) expressed on immune cells using glycans or glycomimetic ligands [29][30][31] .…”

Section: Introductionmentioning

confidence: 99%

A specific, glycomimetic Langerin ligand for human Langerhans cell targeting

Wamhoff

Bellmann

Bachem

et al. 2018

Preprint

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Langerhans cells are a subset of dendritic cells residing in the epidermis of the human skin. As such, they are key mediators of immune regulation and have emerged as prime targets for novel transcutaneous cancer vaccines. Importantly, the induction of protective T cell immunity by these vaccines requires the efficient and specific delivery of both tumor-associated antigens and adjuvants.Langerhans cells uniquely express Langerin (CD207), an endocytic C-type lectin receptor. Here, we report the discovery of a specific, glycomimetic Langerin ligand employing a heparin-inspired design strategy that integrated NMR spectroscopy and molecular docking. The conjugation of these glycomimetics to liposomes enabled the specific and efficient targeting of Langerhans cells in the human skin. This delivery platform provides superior versatility and scalability over antibody-based approaches and thus addresses current limitations of dendritic cell-based immunotherapies.

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“…Different strategies based on liposomal vesicles were designed with the intention of streamlining these functions: examples include acidic pH-sensitive liposomes (Lp) (6, 7), cationic Lp (8, 9), and the inclusion of immunomodulators, such as TLR ligands (10, 11). Liposomal preparations including membranotropic peptides and bacteria pore-forming proteins (PFPs) also were investigated as novel cytosol-delivery systems for cross-priming cytotoxic CD8 + T cells (12, 13).…”

mentioning

confidence: 99%

Novel Adjuvant Based on the Pore-Forming Protein Sticholysin II Encapsulated into Liposomes Effectively Enhances the Antigen-Specific CTL-Mediated Immune Response

Laborde

Sanchez-Ferras

Luzardo

et al. 2017

The Journal of Immunology

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Vaccine strategies to enhance CD8+ CTL responses remain a current challenge because they should overcome the plasmatic and endosomal membranes for favoring exogenous Ag access to the cytosol of APCs. As a way to avoid this hurdle, sticholysin (St) II, a pore-forming protein from the Caribbean Sea anemone Stichodactyla helianthus, was encapsulated with OVA into liposomes (Lp/OVA/StII) to assess their efficacy to induce a CTL response. OVA-specific CD8+ T cells transferred to mice immunized with Lp/OVA/StII experienced a greater expansion than when the recipients were injected with the vesicles without St, mostly exhibiting a memory phenotype. Consequently, Lp/OVA/StII induced a more potent effector function, as shown by CTLs, in vivo assays. Furthermore, treatment of E.G7-OVA tumor-bearing mice with Lp/OVA/StII significantly reduced tumor growth being more noticeable in the preventive assay. The contribution of CD4+ and CD8+ T cells to CTL and antitumor activity, respectively, was elucidated. Interestingly, the irreversibly inactive variant of the StI mutant StI W111C, encapsulated with OVA into Lp, elicited a similar OVA-specific CTL response to that observed with Lp/OVA/StII or vesicles encapsulating recombinant StI or the reversibly inactive StI W111C dimer. These findings suggest the relative independence between StII pore-forming activity and its immuno-modulatory properties. In addition, StII-induced in vitro maturation of dendritic cells might be supporting these properties. These results are the first evidence, to our knowledge, that StII, a pore-forming protein from a marine eukaryotic organism, encapsulated into Lp functions as an adjuvant to induce a robust specific CTL response.

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

Cited by 62 publications

References 57 publications

Monophosphoryl Lipid A‐Adjuvanted Virosomes with Ni‐Chelating Lipids for Attachment of Conserved Viral Proteins as Cross‐Protective Influenza Vaccine

Monophosphoryl Lipid A‐Adjuvanted Virosomes with Ni‐Chelating Lipids for Attachment of Conserved Viral Proteins as Cross‐Protective Influenza Vaccine

A specific, glycomimetic Langerin ligand for human Langerhans cell targeting

Novel Adjuvant Based on the Pore-Forming Protein Sticholysin II Encapsulated into Liposomes Effectively Enhances the Antigen-Specific CTL-Mediated Immune Response

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