• Vaccine Name: MUC1-KLH Vaccine/QS21
• Target Pathogen: Cancer
• Target Disease: Cancer
• Vaccine Ontology ID: VO_0007423
• Type: Conjugate vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: Human
• Antigen: MUC1 1.5 VNTRs, 30 aa: VTSAPDTRPAPGSTAPPAHGVTSAPDTRPA (Adluri et al., 1999)
• MUC1 gene engineering:
  • Type: Recombinant protein preparation
  • Description: (Gathuru et al., 2005)
  • Detailed Gene Information: Click Here.
• Adjuvant: QS-21 (Adluri et al., 1999)
• Preparation: MUC1 peptide was covalently conjugated to KLH using an MBS linker (Adluri et al., 1999)
• Immunization Route: subcutaneous injection
• Description: A synthetic 30 amino acid MUC1 peptide vaccine [(C)VTSAPDTRPAPGSTAPPAHGVTSAPDTRPA] representing 1.5 tandem repeats of the 20 aa MUC1 sequence, conjugated to keyhole limpet hemocyanin (KLH) via MBS linker at a molar ratio of 540:1, and co-administered with QS-21 saponin adjuvant (100 µg each) in breast cancer patients with AJCC stage I–III disease and rising CA15.3 or CEA markers, or stage IV disease currently free of disease. Vaccination induced high titer IgM (peak titers 1:1280–1:20,480) and IgG (peak titers 1:2560–1:10,240) antibodies against the MUC1 peptide in all six breast cancer patients. IgM reactivity against MUC1-positive MCF-7 tumor cells was moderate in four of six patients (59.7–91.4% positive cells) and IgG reactivity was weak in three of six patients (24.3–38.1% positive cells) by FACS analysis, compared to strong reactivity of control mAb HMFG-2 (75%). Inhibition ELISA revealed that anti-MUC1 IgM antibodies in all six patients were directed exclusively against the APDTRPA epitope at the C-terminal end, with no inhibition seen with APDTR, APDTRP, or PDTRPA alone. IgG antibodies showed preferential reactivity with terminal APDTRPA but also some mid-peptide APDTRPA recognition. The restricted epitope specificity and inaccessibility of terminal APDTRPA in the β-turn secondary structure of native tumor MUC1 are proposed to explain the weak tumor cell reactivity of these high-titer sera (Adluri et al., 1999, Ref4162:NCIT_C11845).

Human Response

• Immune Response: DHBcAg was as effective as KLH in generating antibody responses. There were high IgG titers (1/6,553,600) when using same carrier throughout, while the titers were lower when switching carriers. Both carriers generated antibodies that bound to MUC1+ cancer cells. No significant complement-mediated cytotoxicity was observed (Gathuru et al., 2005).