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Vaccine Detail

Autologous MUC1 peptide-pulsed DC vaccine
Vaccine Information
  • Vaccine Name: Autologous MUC1 peptide-pulsed DC vaccine
  • Target Pathogen: Cancer
  • Target Disease: Cancer
  • Type: Dendritic cell vaccine
  • Status: Clinical trial
  • Host Species for Licensed Use: Human
  • Antigen: MUC1 (Rong et al., 2012)
  • Immunization Route: Intradermal injection (i.d.)
  • Description: An autologous dendritic cell vaccine prepared from patient peripheral blood monocytes cultured with GM-CSF (800 U/ml) and IL-4 (1,000 U/ml) for 5 days to generate premature DCs, pulsed with MUC1 20-mer peptide (PDTRPAPGSTAPPAHGVTSA, 50 μg/ml) for 16 h overnight, then matured with TNF-α (10 ng/ml) and harvested on day 7. Final vaccine consisted of 3-6 × 10⁶ mature DCs administered intradermally. In a phase I trial in 7 pancreatic ductal adenocarcinoma patients with recurrent lesions or metastasis after surgery (6 Stage IV, 1 Stage III, all MUC1-positive by immunohistochemistry), vaccination demonstrated no autoimmunity and grade II fever in 2/7 (28.6%) with local erythema. Immunologically, 2/7 (28.6%) patients showed significant increases in IFN-γ and granzyme B secreting PBMCs (P<0.05) to MUC1 peptide by ELISPOT assay, while 5/7 (71.4%) were non-responders. Clinically, 100% experienced disease progression within 3 months with no tumor regressions, disease stabilizations, or objective clinical tumor responses. DC generation was successful in all patients with yields of 3.3 ± 1.6% (range 1-6%) from starting PBMCs and viabilities of 95-98%. Mature DCs expressed high levels of CD209 (66 ± 10%), HLA-DR (96 ± 1%), and CD86 (94 ± 4.3%) with low CD14 (4 ± 2.6%). MUC1 is a tumor-associated antigen that is overexpressed in pancreatic adenocarcinomas (Rong et al., 2012).
Host Response
References