Adoptive Immunotherapy for Pancreatic Cancer Using MUC1 Peptide-pulsed Dendritic Cells and Activated T Lymphocytes

Overall Survival (1)

Overall Survival

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Summary

This trial investigated the efficacy and safety of this DC-based adjuvant immunotherapy with patients with Hepatocellular cancer. The results show that adjuvant immunotherapy with DC vaccine reduces the risk of tumour recurrence in HCC patients who underwent standard treatment modalities other than RFA. Baseline IL-15 might be a candidate biomarker for DC-based HCC immunotherapy.

Patients characteristics

156 patients who were histologically diagnosed with hepatocellular carcinoma (HCC). Patients who achieved complete remission after one or two treatment(s), including surgical resection, radiofrequency ablation (RFA), trans-arterial chemoembolization (TACE), and percutaneous ethanol injection (PEI) for HCC of stage between I and III within 4 weeks before this trial.

Methodology

Patients were randomly assigned to either the immunotherapy (n =77) or the control group (n=79).
Vaccine generation
Autologous DCs were generated from peripheral blood mononuclear cells (PBMC) obtained from the HCC patients through leukapheresis at each center 2 weeks before the first vaccination. Monocytes were separated from the patient PBMC and cultured with supplements of granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 5 days. On day 5, immature DCs were harvested and pulsed with CTP24-fused human AFP, GPC-3, and MAGE-1 recombinant proteins, and then matured in the presence of a cytokine cocktail consisting of IL-6, IL-1b, tumor necrosis factor-a, prostaglandin E2, interferon (IFN)g, OK432, and poly I:C for 2 days. On day 7, the DCs were harvested, washed, and resuspended in cryopreserving solution. Finally, fully equipped DC vaccines were packed into a sterile glass vial, sealed with a snap-cap, and stored at an ultralow cryopreservation system.

Treatment

Multiple TAA-pulsed DC vaccine (3 x 107 cells/injection) was injected subcutaneously into the thigh near the inguinal lymph nodes. Topical toll-like receptor-7 (TLR-7) agonist (Imiquimod) was applied around the injection site for two consecutive days before injection. Patients received DC vaccine six times over 14 weeks (four times every 2 week and then two times every 4 week). Vital signs were monitored during and after each vaccine injection.

Results

Recurrence-free survival analysis
Among the 144 patients in the efficacy population, 69 experienced tumor recurrence or death by the time of data cut-off: 33 (47.8%) in the immunotherapy group and 35 (46.7%) in the control group. Among the subgroup of 62 patients who received surgical resection (30 immunotherapy and 32 control), the immunotherapy patients showed a trend toward prolonged RFS.
When assessed among the 56 surgically resected patients who completed the full treatment as per- protocol (PP) analysis, the RFS was significantly improved by immunotherapy. In a subgroup of 10 patients, who received TACE for HCC (5 immunotherapy and 5 control), none in immunotherapy group experienced tumor recurrence during the study period, compared with four of five controls.
Safety
Treatment-emergent adverse events (TEAEs) occurred in 108 patients (74.0%) in the safety population (n=146) and immunotherapy patients (69/70, 98.6%) experienced TEAEs more frequently than controls (39/76, 51.3%). However, the frequency of serious TEAEs between the two groups was comparable (14.2% immunotherapy vs. 17.1% control). Sixty-five immunotherapy patients (92.9%) experienced a total of 503 TEAEs counted related to study drug; 502 (99.8%) were mild to moderate (grade 1 or 2) and 1 (0.2%) was grade 3 (injection site ulcer), and there was no drug-related deaths.

Conclusion

In conclusion, this study demonstrated that active adjuvant immunotherapy using a TAA-pulsed DC vaccine can prolong RFS in patients with HCC who have achieved complete remission by treatment modalities other than RFA. The DC vaccine was associated with a higher frequency of TEAE, but not with severe TEAE.

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Scientific article publishing date: 6/28/2017

Immucura identifier BSC22_381EN

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