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Design of a MUC1-based tricomponent vaccine adjuvanted with FSL-1 for cancer immunotherapy.

ABSTRACT: MUC1 is an attractive target for cancer vaccines as a result of its over-expression and aberrant glycosylation pattern on many tumor cells. However, the low immunogenicity of MUC1 and immune tolerance have limited its application. Herein, we designed MUC1-based tricomponent antitumor vaccines adjuvanted with fibroblast stimulating lipopeptide 1 (FSL-1). Immunological results indicate that the glycosylated tricomponent vaccine candidate has elicited both humoral and cellular immune responses. The induced antibodies could effectively bind to MCF-7. Furthermore, the vaccine exhibited an obvious reduction in tumour burden.

SUBMITTER: Li M

PROVIDER: S-EPMC6991171 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Design of a MUC1-based tricomponent vaccine adjuvanted with FSL-1 for cancer immunotherapy.

Li Mingjing M Wang Zhaoyu Z Yan Bocheng B Yin Xiaona X Zhao Yue Y Yu Fan F Meng Meng M Liu Yonghui Y Zhao Wei W

MedChemComm 20190712 12

MUC1 is an attractive target for cancer vaccines as a result of its over-expression and aberrant glycosylation pattern on many tumor cells. However, the low immunogenicity of MUC1 and immune tolerance have limited its application. Herein, we designed MUC1-based tricomponent antitumor vaccines adjuvanted with fibroblast stimulating lipopeptide 1 (FSL-1). Immunological results indicate that the glycosylated tricomponent vaccine candidate has elicited both humoral and cellular immune responses. The ...[more]

PMID: 32133105

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Design, Synthesis, and Preliminary Immunological Studies of MUC1-Based Antitumor Vaccines Adjuvanted with <i>R</i>- and <i>S</i>-FSL-1.

Project description:Fibroblast stimulating lipopeptide 1 (FSL-1) is the ligand of TLR2 and TLR6 and can be used as the vaccine adjuvant to prepare antitumor vaccines. However, FSL-1 is a stereoisomeric mixture that contains the R stereoisomer and S stereoisomer, and it is still unclear which stereoisomer has better adjuvant activities. In this work, we designed and synthesized MUC1-based antitumor vaccines adjuvanted with the stereoisomers R-FSL-1 and S-FSL-1, which were synthesized from the stereoisomeric building blocks R-Fmoc-Pam2Cys-OH and S-Fmoc-Pam2Cys-OH, respectively. Immunological evaluation indicated that both R-FSL-1 and S-FSL-1 can be used as adjuvants for the construction of MUC1-based antitumor vaccines, with R-FSL-1 showing a better adjuvant effect than S-FSL-1.

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Tricomponent immunopotentiating system as a novel molecular design strategy for malaria vaccine development.

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Advances in MUC1-Mediated Breast Cancer Immunotherapy.

Project description:Breast cancer (BRCA) is the leading cause of death from malignant tumors among women. Fortunately, however, immunotherapy has recently become a prospective BRCA treatment with encouraging achievements and mild safety profiles. Since the overexpression and aberrant glycosylation of MUC1 (human mucin) are closely associated with BRCA, it has become an ideal target for BRCA immunotherapies. In this review, the structure and function of MUC1 are briefly introduced, and the main research achievements in different kinds of MUC1-mediated BRCA immunotherapy are highlighted, from the laboratory to the clinic. Afterward, the future directions of MUC1-mediated BRCA immunotherapy are predicted, addressing, for example, urgent issues in regard to how efficient immunotherapeutic strategies can be generated.

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Biomaterials for vaccine-based cancer immunotherapy.

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A Phase I Trial Using a Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury)-Based Immunotherapy Vaccine Regimen in Patients with Advanced Cancer.

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Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice.

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Systems serology-based comparison of antibody effector functions induced by adjuvanted vaccines to guide vaccine design.

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Computational biology and artificial intelligence in mRNA vaccine design for cancer immunotherapy.

Project description:Messenger RNA (mRNA) vaccines offer an adaptable and scalable platform for cancer immunotherapy, requiring optimal design to elicit a robust and targeted immune response. Recent advancements in bioinformatics and artificial intelligence (AI) have significantly enhanced the design, prediction, and optimization of mRNA vaccines. This paper reviews technologies that streamline mRNA vaccine development, from genomic sequencing to lipid nanoparticle (LNP) formulation. We discuss how accurate predictions of neoantigen structures guide the design of mRNA sequences that effectively target immune and cancer cells. Furthermore, we examine AI-driven approaches that optimize mRNA-LNP formulations, enhancing delivery and stability. These technological innovations not only improve vaccine design but also enhance pharmacokinetics and pharmacodynamics, offering promising avenues for personalized cancer immunotherapy.

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