Strategies for Synthesizing and Enhancing the Immune Response of Cancer Vaccines Based on MUC1 Glycopeptide Antigens

Liu, Yin; Zhou, Yang; Hong, Sihui; Ding, Feiqing; Cai, Hui

doi:10.1002/cbic.202200805

Cited by 4 publications

(1 citation statement)

References 127 publications

(216 reference statements)

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“…In recent years, antitumor vaccines have exhibited tremendous potential as an effective therapeutic approach in the treatment of cancer. − Human mucin-1 (MUC1) is an important tumor-associated antigen (TAA) that is aberrantly overexpressed on various epithelial cancer cells, making it a promising target for cancer immunotherapy. , In fact, the extracellular portion of MUC1 contains a variable number of tandem repeat (VNTR) of the amino acid sequence (HGVTSAPDTRPAPGSTAPPA), which offers five potential O-glycosylation sites and can serve as a promising B-cell epitope for a MUC1-targeted antitumor vaccine. − These O-glycans also play an important role in maintaining the structural and functional properties of glycoproteins. , However, as an endogenous antigen and hapten, MUC1 glycopeptide exhibits weak immunogenicity, leading to a restricted capacity to elicit a potent immune response, which significantly constrains its clinical applications in medicine.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Zhou,

Zhang,

Wen

et al. 2024

J. Med. Chem.

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Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as a carrier, in which the TLR1/2 agonist Pam 3 CSK 4 was conjugated to the N-terminus of MUC1-loaded carrier protein BSA through pyridoxal 5′phosphate-mediated transamination reaction. The resulting Pam 3 CSK 4 − BSA-MUC1 conjugate was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells. The results indicated that this lipidated protein carrier significantly enhanced antigen uptake by APCs and obviously augmented the retention of the vaccine at the injection site. Compared with the BSA-MUC1 and BSA-MUC1 + Pam 3 CSK 4 groups, Pam 3 CSK 4 −BSA-MUC1 evoked 22-and 11-fold increases in MUC1-specific IgG titers. Importantly, Pam 3 CSK 4 −BSA-MUC1 elicited robust cellular immunity and significantly inhibited tumor growth. This is the first time that lipidated protein was constructed to enhance antigen immunogenicity, and this universal carrier platform exhibits promise for utilization in various vaccines, holding the potential for further clinical application.

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Section: Introductionmentioning

confidence: 99%

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Zhou,

Zhang,

Wen

et al. 2024

J. Med. Chem.

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Tumor-associated carbohydrate antigens of MUC1 – Implication in cancer development

Radziejewska

2024

Biomedicine & Pharmacotherapy

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Exploring Photoredox Catalytic Reactions as an Entry to Glycosyl-α-amino Acids

Bretón,

Oroz,

Torres

et al. 2024

ACS Omega

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The synthesis of glycosyl-α-amino acids presents a significant challenge due to the need for precise glycosidic linkages connecting carbohydrate moieties to amino acids while maintaining stereo-and regiochemical fidelity. Classical methods relying on ionic intermediates (2e − ) often involve intricate synthetic procedures, particularly when dealing with 2-N-acetamido-2-deoxyglycosides linked to α-amino acids�a crucial class of glycoconjugates that play important biological roles. Considering the growing prominence of photocatalysis, this study explores various photoredox catalytic approaches to achieving glycosylation reactions. Our focus lies on the notoriously difficult case of 2-Nacetamido-2-deoxyglycosyl-α-amino acids, which could be obtained efficiently by two methodologies that involved, on the one hand, photoredox Giese reactions using a chiral dehydroalanine (Dha) as an electron density-deficient alkene in these radical 1,4-additions and, on the other hand, photoredox glycosylations using selenoglycosides as glycosyl donors and hydroxyl groups of protected amino acids as acceptors.

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Strategies for Synthesizing and Enhancing the Immune Response of Cancer Vaccines Based on MUC1 Glycopeptide Antigens

Cited by 4 publications

References 127 publications

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Tumor-associated carbohydrate antigens of MUC1 – Implication in cancer development

Exploring Photoredox Catalytic Reactions as an Entry to Glycosyl-α-amino Acids

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