Synthesis, conformational analysis and <i>in vivo</i> assays of an anti-cancer vaccine that features an unnatural antigen based on an sp<sup>2</sup>-iminosugar fragment

Bermejo, Iris A.; Navo, Claudio D.; Castro‐López, Jorge; Guerreiro, Ana; Jiménez‐Moreno, Ester; Sánchez-Fernández, Elena M.; García-Martín, Fayna; Hinou, Hiroshi; Nishimura, Shin‐Ichiro; Fernández, José Manuel Garcı́a; Mellet, Carmen Ortiz; Avenoza, Alberto; Busto, Jesús H.; Bernardes, Gonçalo J. L.; Hurtado‐Guerrero, R.; Peregrina, Jesús M.; Corzana, Francisco

doi:10.1039/c9sc06334j

Cited by 28 publications

(29 citation statements)

References 74 publications

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“…The rationale for choosing CpG-ODN as an adjuvant is that it has a strong agonistic nature for TLR9, which induces Th1-biased immune responses. 33,34 Studies have been conducted to target MUC1 using various innovative platforms, [35][36][37][38][39][40][41][42][43][44][45] findings that the Ala-Pro-Asp-Thr-Arg-Pro (APDTRP) region is the minimum immunogenic epitope of MUC1 responsible for strong tumor cell recognition. 46 Based on this information, we prepared a Tn-glycopeptide (TnG) with an amine linker for nanostructure-mediated immune activity.…”

Section: Resultsmentioning

confidence: 99%

Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

Turaskar

Chaudhary

Kikkeri

2021

Preprint

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T-cell-dependent immunomodulation of carbohydrate antigens under benign conditions is the most promising approach for carbohydrate-based vaccine development. However, to achieve such adaptive immune responses, well-defined multifunctional nanocarriers loaded with immunogenic materials must be explored. Current efforts to use gold nanoparticles (AuNPs) as antigen carriers in vaccine development have conveniently introduced considerable diversity. Here, we show that the shape of AuNPs markedly influences carbohydrate-based antigen processing in murine dendritic cells (mDCs) and subsequent T-cell activation. In the study, CpG-adjuvant coated sphere-, rod-, and star-shaped AuNPs were conjugated to the tripodal Tn-glycopeptide antigen to study their DC uptake and the activation of T-cells in the DCs/T-cell co-culture assay. Our results showed that sphere- and star-shaped AuNPs displayed relatively weak receptor-mediated uptake but induced a high level of T helper-1 (Th1) biasing immune responses compared with rod-shaped AuNPs, showing that receptor-mediated uptake and cytokine secretion of nanostructures are two independent mechanisms. Significantly, the shapes of AuNPs and antigen/adjuvant conjugation synergistically work together to modulate the effective anti-Tn-glycopeptide immunoglobulin (IgG) antibody response after in vivo administration of the AuNPs. These results show that by varying the shape parameter, one can alter the immunomodulation, leading to the development of carbohydrate vaccines.

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Section: Resultsmentioning

confidence: 99%

Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

Turaskar

Chaudhary

Kikkeri

2021

Preprint

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“…Current applications focus on site-specific drug/gene delivery and protein separation and analysis. Considering the avant-garde developments in CD chemistry, glycobiology and nanotechnology, a much broader range of progress is expected in the near future from their synergistic blend, including fields as diverse as catalysis [199,200], bioremediation [201], sensing [202][203][204][205], diagnostics [206,207], theranostics [208,209], vaccines [210,211] or personalized medicine [212,213]. Structures and schematic representation of the strategy developed by Riela, Lazzala and coworkers to assemble hybrid glycoCD/halloysite nanotubes to achieve functional glyconanomaterials for the co-administration of curcumin (Cur) and silibinin (Sil) in thyroid cancer cells [196,197].…”

Section: Discussionmentioning

confidence: 99%

Cyclodextrin-Based Functional Glyconanomaterials

2020

Self Cite

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Cyclodextrins (CDs) have long occupied a prominent position in most pharmaceutical laboratories as “off-the-shelve” tools to manipulate the pharmacokinetics of a broad range of active principles, due to their unique combination of biocompatibility and inclusion abilities. The development of precision chemical methods for their selective functionalization, in combination with “click” multiconjugation procedures, have further leveraged the nanoscaffold nature of these oligosaccharides, creating a direct link between the glyco and the nano worlds. CDs have greatly contributed to understand and exploit the interactions between multivalent glycodisplays and carbohydrate-binding proteins (lectins) and to improve the drug-loading and functional properties of nanomaterials through host–guest strategies. The whole range of capabilities can be enabled through self-assembly, template-assisted assembly or covalent connection of CD/glycan building blocks. This review discusses the advancements made in this field during the last decade and the amazing variety of functional glyconanomaterials empowered by the versatility of the CD component.

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“…Third, cancerous MUC1 has a different structure from normal MUC1, which is overexpressed only on cancer cells. The fourth and final, specific MUC1 sequence (PDTRP) is one of the most immunogenic epitopes of MUC1, which is the target of SM3 mAb [ 141 ].…”

Section: Trastuzumab-mechanisms Of Actionmentioning

confidence: 99%

“…Data show that MUC1 can be another target, which should be added to target molecules to restore trastuzumab sensitivity since it not only has crosstalk with several oncogenic/mitogenic pathways but also has a role in trastuzumab resistance in BC cells [ 138 , 142 ]. Hence, MUC1 is a good target for mAb, vaccines, and inhibitors [ 141 , 143 ]. For example, studies show that using siRNA MUC1 or anti-MUC1 mAb would make BC cells susceptible to trastuzumab-mediated ADCC [ 23 ].…”

Section: Trastuzumab-mechanisms Of Actionmentioning

confidence: 99%

MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy

et al. 2022

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Although resistance is its major obstacle in cancer therapy, trastuzumab is the most successful agent in treating epidermal growth factor receptor 2 positive (HER2 +) breast cancer (BC). Some patients show resistance to trastuzumab, and scientists want to circumvent this problem. This review elaborately discusses possible resistance mechanisms to trastuzumab and introduces mucin 1 (MUC1) as a potential target efficient for overcoming such resistance. MUC1 belongs to the mucin family, playing the oncogenic/mitogenic roles in cancer cells and interacting with several other oncogenic receptors and pathways, such as HER2, β-catenin, NF-κB, and estrogen receptor (ERα). Besides, it has been established that MUC1- Cytoplasmic Domain (MUC1-CD) accelerates the development of resistance to trastuzumab and that silencing MUC1-C proto-oncogene is associated with increased sensitivity of HER2+ cells to trastuzumab-induced growth inhibitors. We mention why targeting MUC1 can be useful in overcoming trastuzumab resistance in cancer therapy.

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Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp²-iminosugar fragment

Abstract: An anti-cancer vaccine based on an unnatural antigen with an sp2-iminosugar fragment.

Cited by 28 publications

References 74 publications

Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

Cyclodextrin-Based Functional Glyconanomaterials

MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy

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Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp2-iminosugar fragment

Abstract: An anti-cancer vaccine based on an unnatural antigen with an sp2-iminosugar fragment.

Cited by 28 publications

References 74 publications

Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

Cyclodextrin-Based Functional Glyconanomaterials

MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy

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Product

Resources

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Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp²-iminosugar fragment