Chemically engineered glycan-modified cancer vaccines to mobilize skin dendritic cells

Duinkerken, Sanne; Li, R.J. Eveline; Haften, Floortje J. van; Gruijl, Tanja D. de; Chiodo, Fabrizio; Schetters, Sjoerd; Kooyk, Yvette van

doi:10.1016/j.cbpa.2019.10.001

Cited by 10 publications

(16 citation statements)

References 49 publications

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“…13,47 Although receptor precipitation impeded complete inhibition of the reporter when exceeding 1 mM 48, titration experiments still allowed the estimation of a millimolar K I value (K I = 1.15 ± 0.01 mM) supporting interactions with the CBS (Figure 3a). Orthogonal assays using direct quantification of 19 F CSPs and relaxation rates R 2 of 48 via its trifluoromethyl group, as well as a 15 N HSQC NMR titration, revealed micromolar K D values in the range determined for Langerin (K D , 19 F CSP = 0.37 ± 0.06 mM, K D , 19 F R 2 filtered = 0.48 ± 0.06 mM, K D , 15 N HSQC = 0.46 ± 0.16 mM) (Figures 3b and S17, Table S6). To confirm the involvement of the Ca 2+ -dependent CBS, we then performed R 2 -filtered NMR experiments under inhibitory conditions and observed that neither high Man concentrations nor EDTA addition completely abrogated binding of 48 to DC-SIGN (Figure 3c).…”

Section: ■ Resultsmentioning

confidence: 99%

“…Using STD NMR and 15 N HSQC NMR experiments in conjunction with molecular docking studies, we explored the suspected dual binding mode in more detail: Initial STD NMR epitope mapping for 48 revealed STD effects for all ligand protons in the presence of DC-SIGN (Figures 3d and S18). This contrasts our findings for Langerin, where 42 showed a binding epitope dominated by saturation transfer to the biphenyl aglycone (Note S3).…”

Section: ■ Resultsmentioning

confidence: 99%

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A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN

et al. 2021

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Dendritic cells (DC) are antigen-presenting cells coordinating the interplay of the innate and the adaptive immune response. The endocytic C-type lectin receptors DC-SIGN and Langerin display expression profiles restricted to distinct DC subtypes and have emerged as prime targets for next-generation immunotherapies and anti-infectives. Using heteromultivalent liposomes copresenting mannosides bearing aromatic aglycones with natural glycan ligands, we serendipitously discovered striking cooperativity effects for DC-SIGN+ but not for Langerin+ cell lines. Mechanistic investigations combining NMR spectroscopy with molecular docking and molecular dynamics simulations led to the identification of a secondary binding pocket for the glycomimetics. This pocket, located remotely of DC-SIGN’s carbohydrate bindings site, can be leveraged by heteromultivalent avidity enhancement. We further present preliminary evidence that the aglycone allosterically activates glycan recognition and thereby contributes to DC-SIGN-specific cell targeting. Our findings have important implications for both translational and basic glycoscience, showcasing heteromultivalent targeting of DCs to improve specificity and supporting potential allosteric regulation of DC-SIGN and CLRs in general.

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Section: ■ Resultsmentioning

confidence: 99%

Section: ■ Resultsmentioning

confidence: 99%

A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN

et al. 2021

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“…However, it remains challenging to target skin-resident immune cells specifically while avoiding off-target effect due to the physical barrier. [98] To troubleshoot this, biodegradable MN patch, [19] injectable hydrogel [18] and implantable scaffold [20] that enable intradermal or transdermal [100] Copyright 2018, American Chemical Society. D) Schematic illustration of mechanism of this NIR-responsive transdermal MN vaccine.…”

Section: Biomaterial-based Targeting Delivery To Skin-resident Apcsmentioning

confidence: 99%

“…However, it remains challenging to target skin‐resident immune cells specifically while avoiding off‐target effect due to the physical barrier. [ 98 ] To troubleshoot this, biodegradable MN patch, [ 19 ] injectable hydrogel [ 18 ] and implantable scaffold [ 20 ] that enable intradermal or transdermal delivery of immunological cues to skin‐resident APCs have been regard as reliable and effective vaccination strategy.…”

Section: Biomaterial‐based Targeting Modulation Of Apcsmentioning

confidence: 99%

Advanced Biomaterials for Cell‐Specific Modulation and Restore of Cancer Immunotherapy

Ruan

Huang

et al. 2022

Advanced Science

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The past decade has witnessed the explosive development of cancer immunotherapies. Nevertheless, low immunogenicity, limited specificity, poor delivery efficiency, and off-target side effects remain to be the major limitations for broad implementation of cancer immunotherapies to patient bedside. Encouragingly, advanced biomaterials offering cell-specific modulation of immunological cues bring new solutions for improving the therapeutic efficacy while relieving side effect risks. In this review, focus is given on how functional biomaterials can enable cell-specific modulation of cancer immunotherapy within the cancer-immune cycle, with particular emphasis on antigen-presenting cells (APCs), T cells, and tumor microenvironment (TME)-resident cells. By reviewing the current progress in biomaterial-based cancer immunotherapy, here the aim is to provide a better understanding of biomaterials' role in targeting modulation of antitumor immunity step-by-step and guidelines for rationally developing targeting biomaterials for more personalized cancer immunotherapy. Moreover, the current challenge and future perspective regarding the potential application and clinical translation will also be discussed.

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“…Glycan modifications can also be used to target shared or neo-antigens to APCs including dendritic cells. 120 Dendritic cells express lectins binding to glycan epitopes. For example, dendritic cells express the lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and Langerin that can be targeted with fucosylated glycans of Lewis-type oligosaccharides.…”

Section: Modalities To Target Tumor-associated Glycansmentioning

confidence: 99%

Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy

Mantuano

Natoli

Zippelius

et al. 2020

J Immunother Cancer

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During oncogenesis, tumor cells present specific carbohydrate chains that are new targets for cancer immunotherapy. Whereas these tumor-associated carbohydrates (TACA) can be targeted with antibodies and vaccination approaches, TACA including sialic acid-containing glycans are able to inhibit anticancer immune responses by engagement of immune receptors on leukocytes. A family of immune-modulating receptors are sialic acid-binding Siglec receptors that have been recently described to inhibit antitumor activity mediated by myeloid cells, natural killer cells and T cells. Other TACA-binding receptors including selectins have been linked to cancer progression. Recent studies have shown that glycan-lectin interactions can be targeted to improve cancer immunotherapy. For example, interactions between the immune checkpoint T cell immunoglobulin and mucin-domain containing-3 and the lectin galectin-9 are targeted in clinical trials. In addition, an antibody against the lectin Siglec-15 is being tested in an early clinical trial. In this review, we summarize the previous and current efforts to target TACA and to inhibit inhibitory immune receptors binding to TACA including the Siglec-sialoglycan axis.

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Chemically engineered glycan-modified cancer vaccines to mobilize skin dendritic cells

Cited by 10 publications

References 49 publications

A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN

A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN

Advanced Biomaterials for Cell‐Specific Modulation and Restore of Cancer Immunotherapy

Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy

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