• Vaccine Name: IgG3-Fc-Conjugated Liposomal Pam3CysSK4-MUC1-Tn Vaccine
• Target Pathogen: Cancer
• Target Disease: Cancer
• Vaccine Ontology ID: VO_0007568
• Type: Conjugate vaccine
• Status: Research
• Host Species for Licensed Use: Mouse
• Host Species as Laboratory Animal Model: Human
• Antigen: MUC1-Tn (Hossain et al., 2019)
• MUC1 gene engineering:
  • Type: Recombinant protein preparation
  • Description: (Hossain et al., 2019)
  • Detailed Gene Information: Click Here.
• Preparation: Murine IgG3-Fc was conjugated to DPPC/cholesterol liposomes via DSPE-PEG-MAL linker, incorporating a covalently linked Pam3CysSK4-MUC1-Tn construct (Hossain et al., 2019).
• Immunization Route: Intraperitoneal injection (i.p.)
• Description: A self-adjuvanting liposomal glycolipopeptide conjugate cancer vaccine composed of MUC1-Tn glycopeptide covalently linked to TLR-2 agonist Pam3-Cys-SK4, rendering the construct self-adjuvanting without requiring exogenous adjuvant, incorporated into DPPC/cholesterol liposomes extruded through 100 nm polycarbonate membranes, conjugated with murine IgG3-Fc domain via DSPE-PEG-MAL linker (~90% conjugation efficiency). IgG3 was selected to exclusively engage activating FcγRI on dendritic cells while avoiding inhibitory FcγRIIb. C57BL/6 mice (n=5/group) received one prime and two boosts intraperitoneally at days 14 and 28. The Fc-conjugated vaccine produced the highest anti-MUC1-Tn antibody titers by ELISA (Fc-conjugated > anti-Rha-targeted > untargeted control). CD4+ T-cell proliferation measured by [³H]-thymidine incorporation was significantly greater in Fc-conjugated mice than both anti-Rha-targeted and control groups at 40 μg/mL MUC1-Tn stimulation. CD8+ T-cells from Fc-conjugated mice produced elevated IFN-γ upon restimulation with MUC1-Tn CD8 epitope peptide compared to untargeted control only. Similarly, specific cytotoxicity against MUC1 epitope-pulsed EL4 lymphoma target cells in a JAM assay (E:T ratio 100:1) was greater in Fc-conjugated mice relative to untargeted control only. Overall, IgG3-Fc targeting enhanced both humoral and cellular immunity comparably to or exceeding the anti-rhamnose antibody targeting approach without dependence on pre-existing natural antibodies (Hossain et al., 2019).

Human Response

• Immune Response: Both the Fc-conjugated vaccine and the human anti-Rha antibody targeting approaches were more effective than the control group, which received only cancer antigen liposomes. The liposomal Fc-conjugated vaccine was better for producing antigen-specific antibodies compared to the liposomal antigen only, and also produced higher antibody titers than Group B, which received the human anti-Rha antibody. Group A, which received the mouse IgG3-Fc-conjugated cancer vaccine, produced more IFN-gamma than the control group, indicating that enhanced uptake and presentation led to greater IFN-gamma secretion. The highest CD4+ T-cell proliferation was observed at 40 ug/mL, where CD4+ T-cells from the Fc-conjugated vaccine group proliferated significantly more than in the other groups. Cytotoxicity induced by primed CD8+ T-cells was also higher in Group A compared to the control group (Hossain et al., 2019).
• Efficacy: This method proved to be as effective as, or superior to, using anti-rhamnose antibodies to target dendritic cells. The study suggests that targeting Fc directly to dendritic cells could serve as an alternative to human anti-Rha for generating effective antigen-primed T-cells. Targeting a cancer vaccine with a specific Fc isotype domain may be a promising strategy for enhancing vaccine immunogenicity at both the humoral and cellular levels (Hossain et al., 2019).