Design, Synthesis, and Bioactivity Evaluation of a TF-Based Cancer Vaccine Candidate Using Lipid A Mimetics As a Built-In Adjuvant

Gao, Lingqiang; Li, Guiqi; Qiu, Cuiping; Ye, Yifan; Li, Xiaohui; Liao, Pan; Ming, Wenbo; Liu, Zhongqiu; Luo, Xiang; Liao, Guochao

doi:10.1021/acs.jmedchem.4c00042

J. Med. Chem.

2024

DOI: 10.1021/acs.jmedchem.4c00042

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Design, Synthesis, and Bioactivity Evaluation of a TF-Based Cancer Vaccine Candidate Using Lipid A Mimetics As a Built-In Adjuvant

Lingqiang Gao,

Guiqi Li,

Cuiping Qiu

et al.

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Fully Synthetic TF-Based Self-Adjuvanting Vaccine Simultaneously Triggers iNKT Cells and Mincle and Protects Mice against Tumor Development

Yang,

Li,

et al. 2024

J. Med. Chem.

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The Thomsen−Friedenreich (TF) antigen has proven to be a promising target for developing novel therapeutic cancer vaccines. Here, a new strategy that TF antigen covalently coupled with KRN7000 and vizantin was developed. The resulting threecomponent vaccine KRN7000-TF-vizantin simultaneously triggers invariant natural killer T (iNKT) cells and macrophage-inducible Ctype lectin (Mincle) signaling pathways, eliciting much stronger TFspecific immune responses than glycoprotein vaccine TF-KLH/alum and the corresponding two-component conjugate vaccines TF-KRN7000 and TF-vizantin. The analysis of IgG isotypes and the secretion of cytokines revealed that KRN7000-TF-vizantin induced Th1/Th2 mixed immune responses, where Th1 was dominant. In vivo experiments demonstrated that KRN7000-TF-vizantin increased the survival rate and survival time of tumor-challenged mice, and surviving mice rejected further tumor attacks without any additional treatment. This work demonstrates that covalently coupled KRN7000 and vizantin could serve as a promising TF-based vaccine carrier for antitumor immune therapy, and KRN7000-TF-vizantin features great potential to be a vaccine candidate.

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Fully Synthetic TF-Based Self-Adjuvanting Vaccine Simultaneously Triggers iNKT Cells and Mincle and Protects Mice against Tumor Development

Yang,

Li,

et al. 2024

J. Med. Chem.

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show abstract

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Design, Synthesis, and Bioactivity Evaluation of a TF-Based Cancer Vaccine Candidate Using Lipid A Mimetics As a Built-In Adjuvant

Cited by 1 publication

References 55 publications

Fully Synthetic TF-Based Self-Adjuvanting Vaccine Simultaneously Triggers iNKT Cells and Mincle and Protects Mice against Tumor Development

Fully Synthetic TF-Based Self-Adjuvanting Vaccine Simultaneously Triggers iNKT Cells and Mincle and Protects Mice against Tumor Development

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