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Vaccine Detail
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Rha-decorated liposomal Pam3Cys-MUC1-Tn vaccine |
| Vaccine Information |
- Vaccine Name: Rha-decorated liposomal Pam3Cys-MUC1-Tn vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (20-mer, TSAPDTRPAPGSTAPPAHGV), Tn at T6 (Karmakar et al., 2016)
- Immunization Route: subcutaneous injection
- Description: A fully synthetic conjugate vaccine composed of a 20-amino acid MUC1 glycopeptide (TSAPDT(GalNAc)RPAPGSTAPPAHGV) from the VNTR region of MUC1, carrying a tumor-associated ?-N-acetylgalactosamine (GalNAc/Tn antigen) at the DTR motif, conjugated to Pam?Cys via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAc) chemistry and incorporated into DPPC/cholesterol liposomes decorated with Rha-TEG-Cholesterol. In C57BL/6 mice pre-immunized with Rha-Ficoll/Imject Alum to generate anti-Rha antibodies (Group D), the Rha-decorated liposomal vaccine produced over 10-fold higher anti-MUC1 antibody titers compared to controls, 4.6- to 10-fold higher CD8? T cell-specific IFN? production, enhanced CD8? T cell proliferation as the only group showing peptide-specific proliferation above background upon in vitro restimulation with the 8-mer CD8? T cell epitope SAPDTnRPA at 25 ?g/mL, and approximately twice the CTL-mediated apoptosis of EL4 tumor cells at both 1:100 and 1:50 target:effector ratios compared to anti-Rha antibody-expressing mice receiving the non-Rha liposomal vaccine (Group B). These results demonstrate that Rha-mediated immune complex formation enhances Fc?R-dependent antigen uptake by dendritic cells, improving MHC class I cross-presentation of an otherwise weakly presented antigen and CD8? T cell priming while maintaining a robust humoral response (Karmakar et al., 2016).
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| Host Response |
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| References |
Karmakar et al., 2016: Karmakar P, Lee K, Sarkar S, Wall KA, Sucheck SJ. Synthesis of a Liposomal MUC1 Glycopeptide-Based Immunotherapeutic and Evaluation of the Effect of l-Rhamnose Targeting on Cellular Immune Responses. Bioconjugate chemistry. 2016; 27(1); 110-120. [PubMed: 26595674].
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