|
|
Vaccine Detail
|
Tetraphenylethylene (TPE)-(alpha-S-GalNAc)3-P30-Tn-MUC1 Tripartite Vaccine |
| Vaccine Information |
- Vaccine Name: Tetraphenylethylene (TPE)-(alpha-S-GalNAc)3-P30-Tn-MUC1 Tripartite Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Gabba et al., 2023)
- Immunization Route: Subcutaneous, Intraperitoneal
- Description: A fully synthetic tripartite glycopeptide vaccine targeting the macrophage galactose-type lectin (MGL) on dendritic cells. The vaccine consists of three components: a trivalent alpha-S-GalNAc glycocluster on a tetraphenylethylene (TPE) scaffold for MGL binding and enhanced dendritic cell uptake, the P30 T helper epitope from tetanus toxoid, and a tumor-associated MUC1 tandem repeat glycopeptide bearing Tn antigens. The TPE glycocluster enhances binding to MGL by approximately tenfold (EC 50 2.65 nM) compared to MUC1 glycopeptide alone and promotes fourfold increased receptor-mediated uptake by dendritic cells. Immunization with this construct induced over sevenfold higher titers of anti-Tn-MUC1 IgG antibodies compared to controls lacking the MGL-targeting glycocluster, with a mixed Th1/Th2 immune response (IgG1:IgG2b:IgG2c = 0.24:0.50:0.26). The antibodies produced recognize native MUC1-positive breast cancer cells and preferentially bind tumor-associated Tn antigens in the immunodominant PDTR region while showing reduced binding to core 2 and core 4 glycan structures typical of healthy cells. Administered with Freund's adjuvant in preclinical mouse studies (Gabba et al., 2023).
|
| Host Response |
|
|
| References |
Gabba et al., 2023: Gabba A, Attariya R, Behren S, Pett C, van der Horst JC, Yurugi H, Yu J, Urschbach M, Sabin J, Birrane G, Schmitt E, van Vliet SJ, Besenius P, Westerlind U, Murphy PV. MUC1 Glycopeptide Vaccine Modified with a GalNAc Glycocluster Targets the Macrophage Galactose C-type Lectin on Dendritic Cells to Elicit an Improved Humoral Response. Journal of the American Chemical Society. 2023; 145(24); 13027-13037. [PubMed: 37279388].
|
|
