• Vaccine Name: MUC1 140mer Peptide Vaccine with GM-CSF or SB-AS2
• Target Pathogen: Cancer
• Target Disease: Cancer
• Vaccine Ontology ID: VO_0004258
• Type: Peptide vaccine
• Status: Research
• Antigen: 7 MUC1 VNTRs (140 aa; 7×GVTSAPDTRPAPGSTAPPAH) (Soares et al., 2001)
• MUC1 gene engineering:
  • Type: Recombinant protein preparation
  • Description: This article lays out the relationship between MUC1 and tumor growth used in cancer vaccines. (Soares et al., 2001)
  • Detailed Gene Information: Click Here.
• Adjuvant: obsolete AS-2 vaccine adjuvant
  • Adjuvant name: obsolete AS-2 vaccine adjuvant
  • VO adjuvant ID: VO_0001336
• Preparation: The 140-aa synthetic MUC1 peptide used for immunization corresponds to seven tandem repeats of a 20-aa sequence from the extracellular tandem repeat domain of MUC1. The peptide vaccine is co-administered with GM-CSF (Soares et al., 2001).
• Immunization Route: Subcutaneous (GM-CSF) / Intramuscular (SB-AS2)
• Description: A synthetic peptide vaccine consisting of a 140-aa MUC1 peptide (seven tandem repeats of the 20-aa sequence GVTSAPDTRPAPGSTAPPAH) administered with either murine GM-CSF (2 µg/mouse, s.c.) or SB-AS2 (MPL + QS-21, oil-in-water emulsion, 50 µl/mouse, i.m.) as adjuvant in C57BL/6 WT and MUC1-Tg mice, immunized once and boosted twice at 3-week intervals. GM-CSF: IgM (both WT and Tg), IgG1/IgG2b (WT only), failure of IgG isotype switching in Tg mice reflecting impaired CD4+ T cell help and/or partial B cell tolerance; SB-AS2: high-titer IgG1/IgG2b/IgG3 in both WT and Tg, 10-fold↓ titer (Tg vs WT), consistent with partial B cell tolerance in Tg mice; SB-AS2 IgG responses T cell-independent in both strains; SB-AS2-induced IgG3 via NK cell-derived IFN-γ (2-3×↑ NK⁺/NK1.1⁺ cells and ↑IFN-γ⁺ NK cells in spleen only, not LN); GM-CSF-induced IgG isotypes IFN-γ independent; no MUC1-specific T cell responses or CTL in either adjuvant group; vaccine-induced Abs recognize native MUC1 on MUC1-transfected T cell lymphoma (RMA-MUC1) tumor surface but confer no protection; tumor rejection: failed in both WT and MUC1-Tg mice following challenge with 5×10⁴ MUC1-transfected T cell lymphoma (RMA-MUC1) cells s.c. (Soares et al., 2001).

Mouse Response

• Host Strain: MUC1-Tg mice (4–6 wk old) on a C57BL/6 background
• Vaccination Protocol: Synthetic MUC1 peptide (100 µg/mouse) coadministered with soluble murine GM-CSF (2 µg/mouse) injected s.c., or synthetic MUC1 peptide (100 µg/mouse) coadministered with SB-AS2 (50 µl/mouse) injected i.m. Mice were immunized once and boosted twice at 3-week intervals (Soares et al., 2001).
• Immune Response: Different vaccine formulations (MUC1 peptide with GM-CSF, MUC1 peptide with SB-AS2, and peptide-pulsed dendritic cells) showed varied immune responses. Only the dendritic cell-based vaccine induced robust T cell-mediated immunity and effective tumor rejection in both wild-type and MUC1-transgenic mice, without causing autoimmunity in MUC1-expressing normal tissues (Soares et al., 2001). The dendritic cell vaccine is described as another entry.
• Challenge Protocol: Ten days after the last boost, the mice were anesthetized with Metofane (Schering-Plough Animal Health, Omaha, NE) and 5 x 10^4 RMA-MUC1 cells injected s.c. in the shaved right hind flank. Tumor growth was monitored every 2–3 days and tumor size determined with calipers (Soares et al., 2001).
• Efficacy: WT and MUC1-Tg mice immunized with MUC1 peptide admixed with either GM-CSF or SB-AS2 failed to reject the tumors. Vaccine-induced Abs recognized native MUC1 on tumor surface but conferred no protection despite high-titer IgG responses (Soares et al., 2001).