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Vaccine Detail
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MUC1-mRNA DC Vaccine and MUC1-CTLs plus Gemcitabine |
| Vaccine Information |
- Vaccine Name: MUC1-mRNA DC Vaccine and MUC1-CTLs plus Gemcitabine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Dendritic cell vaccine
- Status: Clinical trial
- Host Species for Licensed Use: Human
- Antigen: full-length MUC1 mRNA (Shindo et al., 2014)
- Immunization Route: Intradermal injection (i.d.)
- Description: An mRNA-transfected dendritic cell vaccine combining MUC1-mRNA electroporated mature dendritic cells (MUC1-DCs) with adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTLs) and gemcitabine (GEM), evaluated in a retrospective observational study in 42 patients with unresectable or recurrent pancreatic invasive ductal carcinoma. MUC1-DCs were generated from peripheral blood monocytes via GM-CSF and IL-4, matured with TNF-α, and transfected with full-length MUC1-mRNA by electroporation, achieving >95% transfection efficiency; mature DC phenotype was confirmed by markedly increased CD80 (92.1%), CD83 (75.6%), and CD86 (96.5%) expression versus immature DCs (p<0.0001). MUC1-CTLs were induced by co-culture with MUC1-expressing pancreatic cancer cell line YPK-1 with IL-2 stimulation, demonstrating MUC1-specific HLA-unrestricted cytotoxicity confirmed by anti-CD8 (76.9%), anti-CD4 (26.9%), and anti-MUC1 (64.1%) inhibition with no MHC class I inhibition. Treatment achieved MST 13.9 months and 1-year survival 51.1%, compared to historical GEM monotherapy controls (5.7 months, 18%; Burris et al., 1997), with DCR 61.9% (1 CR, 3 PR, 22 SD). Patients receiving both high-dose MUC1-DCs (≥1×10⁷ cells/injection) and MUC1-CTLs (≥3×10⁸ cells/injection) achieved 1-year survival 66.7% vs. 10.4% and MST 16.5 vs. 5.7 months (p=0.0002), with DC dose independently predicting clinical response (p=0.0015). Liver metastasis developed in only 5 of 35 (14%) baseline liver metastasis-free patients. Responders demonstrated significantly reduced MDSCs (10.2±1.6% vs. 21.9±4.0%, p=0.043) and Tregs (0.57±0.18% vs. 1.33±0.41%, p=0.0495), alongside increasing MUC1-specific IFN-γ responses (6.8±2.3 → 23.2±13.9 spots across treatment cycles). No AIT-related adverse events were observed; grade 3/4 toxicities were attributable to GEM (neutropenia 31%, anorexia 14.3%)(Shindo et al., 2014).
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| Host Response |
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| References |
Shindo et al., 2014: Shindo Y, Hazama S, Maeda Y, Matsui H, Iida M, Suzuki N, Yoshimura K, Ueno T, Yoshino S, Sakai K, Suehiro Y, Yamasaki T, Hinoda Y, Oka M. Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer. Journal of translational medicine. 2014; 12; 175. [PubMed: 24947606].
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