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Vaccine Detail
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Autologous DC vaccine pulsed with Tn-MUC1 100-mer glycopeptide and KLH |
| Vaccine Information |
- Vaccine Name: Autologous DC vaccine pulsed with Tn-MUC1 100-mer glycopeptide and KLH
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Dendritic cell vaccine
- Status: Clinical trial
- Host Species for Licensed Use: Human
- Antigen: MUC1 (Scheid et al., 2016)
- Immunization Route: Intradermal and intranodal
- Description: An autologous dendritic cell vaccine loaded with Tn-MUC1 100-mer glycopeptide and keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. Autologous monocyte-derived dendritic cells are loaded ex vivo with a 100-amino acid synthetic MUC1 glycopeptide bearing Tn carbohydrates (GalNAc-α-O-Ser/Thr) and KLH. The dendritic cells are matured with IL-1β, IL-6, TNF-α, and PGE2, then administered intradermally and intranodally. Vaccination may stimulate CD4+ and CD8+ T-cell responses against tumor cells expressing aberrantly glycosylated MUC1. The Tn-MUC1 glycopeptide contains five tandem repeats of the sequence GVTSAPDTRPAPGSTAPPAH from the human MUC1 VNTR region. Tumor-associated MUC1 is hypoglycosylated with truncated oligosaccharides such as Tn antigen (GalNAc-α-O-Ser/Thr), distinguishing it from normally glycosylated MUC1 on healthy epithelial cells. KLH serves as a positive control antigen to assess immune reactivity. In a phase I/II clinical trial in patients with non-metastatic castrate-resistant prostate cancer (n=16), the vaccine demonstrated safety and induced Tn-MUC1-specific CD4+ and/or CD8+ T-cell responses (predominantly IL-2+ and TNF-α+IL-2+) but no antibody responses in 5 of 7 evaluated patients, with KLH-specific responses in 6 of 7 patients. PSA doubling time significantly improved from 4.6 to 10.5 months in 11 of 16 patients (P=0.037). At 24 months, 3 of 16 patients remained progression-free. Preclinical studies in rhesus macaques demonstrated that Tn-rmMUC1-loaded DCs induced approximately 60% stronger IFN-γ+ T-cell responses compared to Tn-rmMUC1 with adjuvant (Scheid et al., 2016).
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| Host Response |
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| References |
Scheid et al., 2016: Scheid E, Major P, Bergeron A, Finn OJ, Salter RD, Eady R, Yassine-Diab B, Favre D, Peretz Y, Landry C, Hotte S, Mukherjee SD, Dekaban GA, Fink C, Foster PJ, Gaudet J, Gariepy J, Sekaly RP, Lacombe L, Fradet Y, Foley R. Tn-MUC1 DC Vaccination of Rhesus Macaques and a Phase I/II Trial in Patients with Nonmetastatic Castrate-Resistant Prostate Cancer. Cancer immunology research. 2016; 4(10); 881-892. [PubMed: 27604597].
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