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Vaccine Detail
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MUC1/survivin-pulsed, SOCS1-silenced, flagellin-stimulated autologous DC vaccine |
| Vaccine Information |
- Vaccine Name: MUC1/survivin-pulsed, SOCS1-silenced, flagellin-stimulated autologous DC vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Dendritic cell vaccine
- Status: Clinical trial
- Host Species for Licensed Use: Human
- Antigen: MUC1, survivin (Ge et al., 2017)
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Adjuvant:
Flagellin (Ge et al., 2017)
- Immunization Route: Intravenous injection (i.v.)
- Description: An autologous dendritic cell vaccine generated from patient-derived PBMCs via leukapheresis, differentiated into immature DCs over 6 days using GM-CSF and IL-4 in serum-free GMP-certified medium, then modified on day 6 with iAPA cytokine complex (10,000 vp/cell) containing SOCS1-specific siRNA and peptides for flagellin, MUC1, and survivin. Eligibility required histochemical confirmation of both MUC1 and survivin positivity in tumor tissue. DC maturation was confirmed by flow cytometry showing significant upregulation of HLA-DR (14.67% → 57.75%), CD80 (0.99% → 70.46%), CD86 (5.71% → 58.24%), CD40 (1.57% → 37.02%), CD83 (1.91% → 28.83%), and CD54 (90.6% → 99.51%), with downregulation of CD14 (88.3% → 19.88%) and HLA-ABC (97.01% → 92.5%); CCR7 showed no significant change (25.15% → 19.55%, p>0.05). In a 3+3 dose-escalation phase I trial (n=15, resected stage I–IIIA NSCLC), patients received three IV infusions at days 7, 14, and 21 at doses of 1×10⁶, 1×10⁷, or 8×10⁷ cells. No dose-limiting toxicity was observed; all adverse events were grade 1–2, most commonly CRP elevation (46.67%), pyrexia (40%), and myalgia (40%). CD3⁺CD4⁺CD25⁺FoxP3⁺ Treg frequency was significantly decreased from day 14 (p<0.05); CD4⁺, CD8⁺, NKT, iNKT, and NK populations showed no significant change (p>0.05). TNF-α was elevated in 2/15 patients and IL-6 up to 21-fold above baseline in 2/15 patients, both peaking at days 21–28; IL-2, IL-4, IL-10, and IFN-γ were not significantly changed (p>0.05). CEA decreased ~15% and CYFRA21 normalized in the 2 patients with abnormal baseline tumor markers. Quality of life (EORTC QLQ-C30) improved significantly overall (p=0.003) and in the high-dose group specifically (p=0.017), but not significantly in the low- (p=0.785) or middle-dose (p=0.102) groups. In long-term follow-up until February 2017 (~3.5 years post-enrollment), 11/15 patients (73%) remained recurrence-free, 2/15 had progressive disease, and 2/15 died approximately 2 years post-vaccination; dose-dependent recurrence-free survival: 33% (low), 100% (middle), 78% (high dose) (Ge et al., 2017).
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| Host Response |
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| References |
Ge et al., 2017: Ge C, Li R, Song H, Geng T, Yang J, Tan Q, Song L, Wang Y, Xue Y, Li Z, Dong S, Zhang Z, Zhang N, Guo J, Hua L, Chen S, Song X. Phase I clinical trial of a novel autologous modified-DC vaccine in patients with resected NSCLC. BMC cancer. 2017; 17(1); 884. [PubMed: 29268708].
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