Targeting C-type lectin receptors with multivalent carbohydrate ligands

Lepenies, Bernd; Lee, Junghoon; Sonkaria, Sanjiv

doi:10.1016/j.addr.2013.05.007

Cited by 224 publications

(181 citation statements)

References 141 publications

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“…This change in glycosylation exposes de novo tumor-specific and immunogenic glycoepitopes (22). Furthermore, changes in the surface O-glycosylation impact the interactions with APCs, as previous studies have shown that selected glycans can be used as efficient tools for dendritic cell targeting in cancer immunotherapy (23,24).…”

Section: Discussionmentioning

confidence: 99%

Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

Rughetti

Rahimi

Belleudi

et al. 2014

Cancer Immunology Research

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Tumor-associated glycoproteins are a group of antigens with high immunogenic interest: The glycoforms generated by the aberrant glycosylation are tumor-specific and the novel glycoepitopes exposed can be targets of tumor-specific immune responses. The MUC1 antigen is one of the most relevant tumor-associated glycoproteins. In cancer, MUC1 loses polarity and becomes overexpressed and hypoglycosylated. Changes in glycan moieties contribute to MUC1 immunogenicity and can modify the interactions of tumor cells with antigen-presenting cells such as dendritic cells that would affect the overall antitumor immune response. Here, we show that the form of the MUC1 antigen, i.e., soluble or as microvesicle cargo, influences MUC1 processing in dendritic cells. In fact, MUC1 carried by microvesicles translocates from the endolysosomal/HLA-II to the HLA-I compartment and is presented by dendritic cells to MUC1-specific CD8 þ T cells stimulating IFN-g responses, whereas the soluble MUC1 is retained in the endolysosomal/HLA-II compartment independently by the glycan moieties and by the modality of internalization (receptor-mediated or non-receptor mediated). MUC1 translocation to the HLA-I compartment is accompanied by deglycosylation that generates novel MUC1 glycoepitopes. Microvesicle-mediated transfer of tumor-associated glycoproteins to dendritic cells may be a relevant biologic mechanism in vivo contributing to define the type of immunogenicity elicited. Furthermore, these results have important implications for the design of glycoprotein-based immunogens for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

Rughetti

Rahimi

Belleudi

et al. 2014

Cancer Immunology Research

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“…[54b] The inherent low affinity (around micromolar to millimolar) of many carbohydrate-lectin interactions can be overcome by presenting multivalent binding motifs on particle surfaces to yield high-avidity binding. [56] Besides their role as targeting moieties, carbohydrates have gained considerable interest as particle coatings due to their hydrophilic, low-fouling character, which can decrease protein adsorption and nonspecific binding. [55b,121] Recent studies highlighted that nanocarriers decorated with carbohydrates as small as mono-and disaccharides (180-360 Da) maintain their targeting abilities in complex biological environments.…”

Section: Wwwadvancedsciencenewscom Wwwadvhealthmatdementioning

confidence: 99%

“…[55] The typically low binding affinity of carbohydrates to their receptors can be improved by multivalent presentation on a particle surface, thereby resulting in high binding avidity. [56] Galactosyl moieties have been applied to direct particles to asialoglycoprotein receptors, which are dominant on the surface of hepatocellular carcinoma HepG2 cancer cells. [57] Lactosylated particles have also been designed for the targeting and detection of galectin-1, a carbohydrate binding protein that plays a central role in cell proliferation, migration and tumor angiogenesis.…”

Section: Targeting Ligandsmentioning

confidence: 99%

Particle Targeting in Complex Biological Media

Dai

Bertleff‐Zieschang

Braunger

et al. 2017

Adv Healthcare Materials

102

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Over the past few decades, nanoengineered particles have gained increasing interest for applications in the biomedical realm, including diagnosis, imaging, and therapy. When functionalized with targeting ligands, these particles have the potential to interact with specific cells and tissues, and accumulate at desired target sites, reducing side effects and improve overall efficacy in applications such as vaccination and drug delivery. However, when targeted particles enter a complex biological environment, the adsorption of biomolecules and the formation of a surface coating (e.g., a protein corona) changes the properties of the carriers and can render their behavior unpredictable. For this reason, it is of importance to consider the potential challenges imposed by the biological environment at the early stages of particle design. This review describes parameters that affect the targeting ability of particulate drug carriers, with an emphasis on the effect of the protein corona. We highlight strategies for exploiting the protein corona to improve the targeting ability of particles. Finally, we provide suggestions for complementing current in vitro assays used for the evaluation of targeting and carrier efficacy with new and emerging techniques (e.g., 3D models and flow‐based technologies) to advance fundamental understanding in bio‐nano science and to accelerate the development of targeted particles for biomedical applications.

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“…15 Recently, multivalent mannoside and trimannoside analogs have been synthesized and evaluated in order to obtain increased affinity for lectins. 16,17 The isothermal titration microcalorimetry data indicated that tri-and tetravalent trimannoside analogs showed 11-and 35-fold higher K a values for Con A, respectively, in comparison with the parent trimannoside. 16 We have also reported a synthesis of C 3 -symmetric (1/6)-N-acetyl-b-D-glucosamine octadecasaccharide with enhanced antitumor activity against H 22 in the preliminary mice tests.…”

Section: Introductionmentioning

confidence: 99%