Precise protein conjugation technology for the construction of homogenous glycovaccines

Kitowski, Annabel; Corzana, Francisco; Bernardes, Gonçalo J. L.

doi:10.1016/j.ddtec.2020.11.007

“…3 ). Cell factory technologies have been used for glycovaccines production [ 149 ], surpassing low yields, scalability challenges and costs of glycopeptides synthesis using chemical approaches [ 128 , 150 ] (Fig. 3 ).…”

Section: Models For Cancer Glycobiology and Glycoimmunologymentioning

confidence: 99%

A roadmap for translational cancer glycoimmunology at single cell resolution

Peixoto

¹

,

Miranda

²

,

Santos

³

et al. 2022

J Exp Clin Cancer Res

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Cancer cells can evade immune responses by exploiting inhibitory immune checkpoints. Immune checkpoint inhibitor (ICI) therapies based on anti-CTLA-4 and anti-PD-1/PD-L1 antibodies have been extensively explored over the recent years to unleash otherwise compromised anti-cancer immune responses. However, it is also well established that immune suppression is a multifactorial process involving an intricate crosstalk between cancer cells and the immune systems. The cancer glycome is emerging as a relevant source of immune checkpoints governing immunosuppressive behaviour in immune cells, paving an avenue for novel immunotherapeutic options. This review addresses the current state-of-the-art concerning the role played by glycans controlling innate and adaptive immune responses, while shedding light on available experimental models for glycoimmunology. We also emphasize the tremendous progress observed in the development of humanized models for immunology, the paramount contribution of advances in high-throughput single-cell analysis in this context, and the importance of including predictive machine learning algorithms in translational research. This may constitute an important roadmap for glycoimmunology, supporting careful adoption of models foreseeing clinical translation of fundamental glycobiology knowledge towards next generation immunotherapies.

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Non‐Natural MUC1 Glycopeptide Homogeneous Cancer Vaccine with Enhanced Immunogenicity and Therapeutic Activity

Guerreiro,

Compañón,

Lazaris

et al. 2024

Angewandte Chemie

0

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Glycopeptides derived from the glycoprotein mucin‐1 (MUC1) have shown potential as tumor‐associated antigens for cancer vaccine development. However, their low immunogenicity and non‐selective conjugation to carriers present significant challenges for the clinical efficacy of MUC1‐based vaccines. Here, we introduce a novel vaccine candidate based on a structure‐guided design of an artificial antigen derived from MUC1 glycopeptide. This engineered antigen contains two non‐natural amino acids and has an α‐S‐glycosidic bond, where sulfur replaces the conventional oxygen atom linking the peptide backbone to the sugar N‐acetylgalactosamine. The glycopeptide is then specifically conjugated to the immunogenic protein carrier CRM197 (Cross‐Reactive Material 197), a protein approved for human use. Conjugation involves selective reduction and re‐bridging of a disulfide in CRM197, allowing the attachment of a single copy of MUC1. This strategy results in a chemically defined vaccine while maintaining both the structural integrity and immunogenicity of the protein carrier. The vaccine elicits a robust Th1‐like immune response in mice and generates antibodies capable of recognizing human cancer cells expressing tumor‐associated MUC1. When tested in mouse models of colon adenocarcinoma and pancreatic cancer, the vaccine is effective both as a prophylactic and therapeutic use, significantly delaying tumor growth. In therapeutic applications, improved outcomes were….

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Non‐Natural MUC1 Glycopeptide Homogeneous Cancer Vaccine with Enhanced Immunogenicity and Therapeutic Activity

Guerreiro,

Compañón,

Lazaris

et al. 2024

Angew Chem Int Ed

0

View full text Add to dashboard Cite

Glycopeptides derived from the glycoprotein mucin‐1 (MUC1) have shown potential as tumor‐associated antigens for cancer vaccine development. However, their low immunogenicity and non‐selective conjugation to carriers present significant challenges for the clinical efficacy of MUC1‐based vaccines. Here, we introduce a novel vaccine candidate based on a structure‐guided design of an artificial antigen derived from MUC1 glycopeptide. This engineered antigen contains two non‐natural amino acids and has an α‐S‐glycosidic bond, where sulfur replaces the conventional oxygen atom linking the peptide backbone to the sugar N‐acetylgalactosamine. The glycopeptide is then specifically conjugated to the immunogenic protein carrier CRM197 (Cross‐Reactive Material 197), a protein approved for human use. Conjugation involves selective reduction and re‐bridging of a disulfide in CRM197, allowing the attachment of a single copy of MUC1. This strategy results in a chemically defined vaccine while maintaining both the structural integrity and immunogenicity of the protein carrier. The vaccine elicits a robust Th1‐like immune response in mice and generates antibodies capable of recognizing human cancer cells expressing tumor‐associated MUC1. When tested in mouse models of colon adenocarcinoma and pancreatic cancer, the vaccine is effective both as a prophylactic and therapeutic use, significantly delaying tumor growth. In therapeutic applications, improved outcomes were….

show abstract

Precise protein conjugation technology for the construction of homogenous glycovaccines

Cited by 6 publications

References 43 publications

A roadmap for translational cancer glycoimmunology at single cell resolution

A roadmap for translational cancer glycoimmunology at single cell resolution

Non‐Natural MUC1 Glycopeptide Homogeneous Cancer Vaccine with Enhanced Immunogenicity and Therapeutic Activity

Non‐Natural MUC1 Glycopeptide Homogeneous Cancer Vaccine with Enhanced Immunogenicity and Therapeutic Activity

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