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Vaccine Detail
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Pam3CSK4-BSA-MUC1 Liposome Vaccine |
| Vaccine Information |
- Vaccine Name: Pam3CSK4-BSA-MUC1 Liposome Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 13-mer MUC1 (GVTSAPDTRPAPG); Tn at T8 (Zhou et al., 2024)
- Immunization Route: subcutaneous injection
- Description: A semisynthetic conjugate vaccine consisting of a Tn-glycosylated MUC1 glycopeptide conjugated to BSA carrier protein (~9.7 copies/BSA) via squaric acid diethyl ester strategy, with TLR1/2 agonist Pam3CSK4 site-specifically conjugated to the BSA N-terminus via PLP-mediated transamination, subsequently encapsulated in DSPC/cholesterol liposomes (~500 nm) biomimicking tumor cell membrane structure. Administered subcutaneously (200 µL/mouse) on days 1, 15, and 29 (prophylactic) or subcutaneously (peritumorally) on days 8, 12, and 16 (therapeutic). Compared to BSA-MUC1 and BSA-MUC1+Pam3CSK4 controls, Pam3CSK4−BSA-MUC1 elicited 22- and 11-fold increases in MUC1-specific IgG titers respectively, with superior responses to clinically approved Alum and MPLA adjuvants. The vaccine induced Th1-skewed immunity with a 6-fold increase in IgG2a/IgG1 ratio, 65.66% CD80⁺CD86⁺ macrophage activation (mean, n=5), significantly elevated IL-6 (5354 pg/mL) and IL-12 (2578 pg/mL) cytokine secretion, increased CD4⁺ and CD8⁺ central memory T cells, 35% CTL lysis of MCF-7 tumor cells, and elevated IFN-γ and TNF-α from both CD4⁺ and CD8⁺ T cells. The lipidated protein carrier enhanced APC antigen uptake, formed a sustained vaccine depot retaining antigen at the injection site up to at least 72 hours, and achieved >98% liposomal encapsulation efficiency. In therapeutic tumor challenge with B16-MUC1 cells, vaccinated mice exhibited mean tumor volumes below 400 mm³ versus over 1,000 mm³ in control groups on day 30, with 60% survival at day 60 compared to 20% for BSA-MUC1+Pam3CSK4 and 0% for all other groups. The platform is proposed as universal, compatible with alternative immunostimulants (TLR4 agonist GAP-112, iNKT agonist αGalCer) and other weakly immunogenic haptens (STn, GM3, GD2) (Zhou et al., 2024).
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| Host Response |
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| References |
Zhou et al., 2024: Zhou SH, Zhang RY, Wen Y, Zou YK, Ding D, Bian MM, Cui HY, Guo J. Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens. Journal of medicinal chemistry. 2024; 67(8); 6822-6838. [PubMed: 38588468].
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