• Vaccine Name: Recombinant Human MUC1-Oxidized Polymannose-pulsed Autologous Dendritic Cell Vaccine
• Target Pathogen: Cancer
• Target Disease: Cancer
• Vaccine Ontology ID: VO_0007015
• Type: Dendritic cell vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: Human
• Antigen: 3 MUC1 VNTRs, 103 aa total; core repeat: PDTRPAPGSTAPPAHGVTSA (Loveland et al., 2006)
• MUC1 gene engineering:
  • Type: Recombinant protein preparation
  • Description: (Loveland et al., 2006)
  • Detailed Gene Information: Click Here.
• Adjuvant: Oxidized mannan (Loveland et al., 2006)
• Immunization Route: Intradermal and subcutaneous
• Description: A dendritic cell vaccine composed of autologous monocyte-derived dendritic cells pulsed ex vivo with mannan-MUC1 fusion protein (MFP), consisting of a recombinant fusion protein of glutathione-S-transferase (26 kDa) and MUC1 VNTR-containing sequences (103 amino acids, 12 kDa) encoding three copies of the conserved 20-mer VNTR motif plus flanking natural variants, conjugated to oxidized mannan. MUC1 antigen, a high-molecular-weight transmembrane glycoprotein, is overexpressed on many tumor cells (NCIT_C102782). Addition of mannan in this vaccine enhances immune recognition by targeting the mannose receptor on dendritic cells, rapidly traversing the endosome to deliver conjugated MUC1 protein to the MHC class I presentation pathway. When the modified dendritic cells are returned to the patient, they may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the MUC1 antigen, resulting in tumor cell lysis, with both CD4+ and CD8+ T-cell responses generated following immunization. Dendritic cells were generated from leukapheresed PBMCs cultured for 6 days with GM-CSF (500 units/mL) and IL-4 (500 units/mL), pulsed with MFP (10 µg/mL) on day 5, and administered intradermally (10⁷ cells per site, two sites) and subcutaneously (remainder across 2–4 sites) at 4-week intervals for three cycles. In a phase I trial of 10 patients with MUC1+ adenocarcinoma (renal, breast, ovarian/fallopian tube, NSCLC, colon, and esophageal carcinoma), vaccine-specific IFN-γ T-cell responses comprising both CD4+ and CD8+ subsets were induced in all 10 patients at frequencies of approximately 1/1,000 PBMCs after 2–3 injections, sustained at 6–12 months and up to 2–3 years in patients receiving extended therapy. DTH reactions were observed in 9 of 10 patients after the 2nd or 3rd injection, with CD4+ T-cell infiltration confirmed on biopsy in a subset of patients. Low titer IgM anti-VNTR antibody responses were detected in 3 of 10 patients, with IgG seroconversion in 2. Two patients with documented progressive disease at entry (ovarian and renal carcinoma) achieved disease stabilization and continued therapy for over 3 years. Toxicity was grade 1 only (Loveland et al., 2006).

Human Response