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Vaccine Detail
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MUC1 Single Tandem Repeat GPI-anchored mRNA Vaccine [MUC1(1TR)-CD24] |
| Vaccine Information |
- Vaccine Name: MUC1 Single Tandem Repeat GPI-anchored mRNA Vaccine [MUC1(1TR)-CD24]
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: mRNA vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (20 aa, PDTRPAPGSTAPPAHGVTSA) (He et al., 2026)
- Immunization Route: Intramuscular injection (i.m.)
- Description: An mRNA-lipid nanoparticle vaccine encoding a MUC1 single tandem repeat VNTR glycopeptide (PDTRPAPGSTAPPAHGVTSA) fused to CD24 for GPI anchoring to the plasma membrane. The mRNA is formulated in lipid nanoparticles and encodes an initially unglycosylated peptide sequence that undergoes post-translational O-glycosylation by host cell machinery, generating bimodal glycosylation populations that may represent Tn antigen-bearing (GalNAcα1-O-Ser/Thr, hypoglycosylated) and highly O-glycosylated forms, supported by PNGase F and O-glycanase Western blot analysis. The 16A monoclonal antibody showed 30-fold higher affinity for ST(Tn)APPAHG versus non-glycosylated STAPPAHG. The expressed antigen is proposed to localize within cholesterol- and glycosphingolipid-enriched lipid rafts via GPI anchoring, permitting rapid lateral diffusion: MUC1(1TR)-CD24 0.12 μm²/s; MUC1(5TR)-CD24 0.26 μm²/s; compared to transmembrane-anchored MUC1(1TR) 0.03 μm²/s, as measured by TIRFM single-molecule tracking in 293T-COSMC-/- cells (n>750 molecules). GPI-anchored single-repeat epitope display elicited >5-fold higher IFN-γ secretion from 16A-CAR-T cells (effector:target 1:2, 24 h) compared with native transmembrane MUC1, confirmed by intracellular IFN-γ flow cytometry, with the strongest CAR-T cell proliferation observed by microscopy. MUC1(1TR,13aa)-CD24 showed similarly potent stimulation. Tandem repeat configurations were inferior: MUC1(5TR)-CD24 showed >3-fold lower IFN-γ stimulation versus MUC1(1TR)-CD24, supporting parallel epitope display as superior to tandem repeat arrangements (n=3, p<0.05–0.0001). The vaccine targets hypoglycosylated MUC1 expressed in multiple cancers including breast, ovarian, gastric, colorectal, prostate, and lung adenocarcinoma, with tumor specificity associated with aberrant Tn antigen glycosylation absent in normal tissues (He et al., 2026).
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| Host Response |
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| References |
He et al., 2026: He Y, Zhou B, Tong J, Ji Z, Wang N, Lai H, Wang J, Zhu C, Mai X, Xu C, Wang PG, Zhou D. Immunogenicity of mRNA encoded MUC1 glycopeptides toward CAR-T cells. European journal of cell biology. 2026; 105(3); 151543. [PubMed: 42143891].
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