ArticleJournal of the American Chemical Society2018
Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 95 citations in OpenAlex.
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- 4-Formyl-N-Methylpyridinium-Mediated N-Terminal Cysteine Modification/Removal Facilitates One-Pot Multiplex Peptide Ligation.Angewandte Chemie (International ed. in English) · 2026Article
- A Glycopeptide Mosaic Vaccine Elicits Robust Antitumor Immunity by Targeting Glycan Heterogeneity.JACS Au · 2026Article
- Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.The American journal of pathology · 2025Review
- Diphtheria Toxoid-Derived T-Helper Epitope and α-galactosylceramide Synergistically Enhance the Immunogenicity of Glycopeptide Antigen.ACS pharmacology & translational science · 2024Article
- Carbohydrate-Lectin Interactions Reprogram Dendritic Cells to Promote Type 1 Anti-Tumor Immunity.ACS nano · 2024Article
- Inducing Long Lasting B Cell and T Cell Immunity Against Multiple Variants of SARS-CoV-2 Through Mutant Bacteriophage Qβ-Receptor Binding Domain Conjugate.Advanced healthcare materials · 2024Article
- Characterizing and forecasting neoantigens-resulting from MUC mutations in COAD.Journal of translational medicine · 2024Article
- Enhancing Protective Antibodies against Opioids through Antigen Display on Virus-like Particles.Bioconjugate chemistry · 2024Article
- Development of NHAcGD2/NHAcGD3 conjugates of bacteriophage MX1 virus-like particles as anticancer vaccines.RSC advances · 2024Article
- Glycan-costumed virus-like particles promote type 1 anti-tumor immunity.bioRxiv : the preprint server for biology · 2024Article
- Stereoselective Synthesis of Sialyl LewisAngewandte Chemie (International ed. in English) · 2023Article
- TLR Agonists Delivered by Plant Virus and Bacteriophage Nanoparticles for Cancer Immunotherapy.Bioconjugate chemistry · 2023Article
- Virus-like Particle (VLP) Vaccines for Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Peptide Vaccines as Therapeutic and Prophylactic Agents for Female-Specific Cancers: The Current Landscape.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Vaccine adjuvants: mechanisms and platforms.Signal transduction and targeted therapy · 2023Review
- Development of synthetic, self-adjuvanting, and self-assembling anticancer vaccines based on a minimal saponin adjuvant and the tumor-associated MUC1 antigen.Chemical science · 2023Article
- Review
- Developing Next-Generation Protein-Based Vaccines Using High-Affinity Glycan Ligand-Decorated Glyconanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
Human mucin-1 (MUC1) is a highly attractive antigen for the development of anticancer vaccines. However, in human clinical trials of multiple MUC1 based vaccines, despite the generation of anti-MUC1 antibodies, the antibodies often failed to exhibit much binding to tumor presumably due to the challenges in inducing protective immune responses in the immunotolerant environment. To design effective MUC1 based vaccines functioning in immunotolerant hosts, vaccine constructs were first synthesized by covalently linking the powerful bacteriophage Qβ carrier with MUC1 glycopeptides containing 20-22 amino acid residues covering one full length of the tandem repeat region of MUC1. However, IgG antibodies elicited by these first generation constructs in tolerant human MUC1 transgenic (Tg) mice did not bind tumor cells strongly. To overcome this, a peptide array has been synthesized. By profiling binding selectivities of antibodies, the long MUC1 glycopeptide was found to contain immunodominant but nonprotective epitopes. Critical insights were obtained into the identity of the key protective epitope. Redesign of the vaccine focusing on the protective epitope led to a new Qβ-MUC1 construct, which was capable of inducing higher levels of anti-MUC1 IgG antibodies in MUC1.Tg mice to react strongly with and kill a wide range of tumor cells compared to the construct containing the gold standard protein carrier, i.e., keyhole limpet hemocyanin. Vaccination with this new Qβ-MUC1 conjugate led to significant protection of MUC1.Tg mice in both metastatic and solid tumor models. The antibodies exhibited remarkable selectivities toward human breast cancer tissues, suggesting its high translational potential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.