Postoperative dendritic cell vaccine plus activated T-cell transfer improves the survival of patients with invasive hepatocellular carcinoma

Prospective recurrence-free survival

Prospective recurrence-free survival

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Summary

This study investigated the clinical utilization of an autologous tumor lysate-pulsed dendritic cell vaccine plus ex vivo activated T cell transfer (ATVAC) in an adjuvant setting for postoperative Hepatocellular carcinoma. The findings suggest A postoperative DC vaccine plus activated T cell transfer would be a feasible and effective treatment for preventing recurrence in HCC patients.

Patients characteristics

• 94 patients enrolled In this study with an Invasive Hepatocellular Carcinoma (HCC) with 2.5 cm diameter or larger. 42 patients received adjuvant Immunotherapy and 53 patients with surgery alone.
• There was no critical surgical morbidity or mortality in the enrolled
patients and no significant differences in patients characteristics.

Methodology

• Autologous peripheral blood mononuclear cells were obtained by leukapheresis performed on a Heamonetics CCS.
• Leukapheresis consists of 4 cycles, in which 1.5-2L blood were collected containing 1×109 cells per patient.
• PBMCs were plated in AIM-V medium at 1×107 cell/mL total volume of 50mL in each flask for 2 hours at 370C in 5% CO2
• Non-adherent cells were removed for further use. Adherent cells were cultured in AIM-V medium containing GM-CSF and IL-4.
• On day 6, the DCs were harvested from the flask and resuspended at 1×106 cells/mL in AIM-V medium containing GM-CSF, IL-4 and recombinant TNF- and pulsed with tumor lysate with same number of DCs to adjust at a 1:1 cell equivalent ratio and 1mL of KLH diluted in PBS.
• DCs were then incubated for 24 hours at 37oC in 5% CO2 atmosphere. DC were harvested and adjusted to a total volume of 0.5mL of saline for Intradermal administration.

Treatment

Each patient was vaccinated Intradermally (ID) near inguinal nodal region.

Results

• The vaccine was well-tolerated without any treatment associated adverse events of grade 3 or higher
• 22 of 42 patients with adjuvant immunotherapy developed grade I local skin reaction with redness at the injection site, no ulceration was seen.
• No high-grade fever, fatigue, diarrhea, rash or itching was observed.
• No hematologic, cardiovascular, hepatic or renal toxicity was
observed during and after the treatment.
• Postoperative 5 year recurrence free survival of patients received
surgery with DC vaccine was 35.7% with median RFS of 24.5 months
• The 5 year RFS of patients having surgery alone was 11.5% with
median RFS of 12.6 months (p=0.011)
• Postoperative with DCV overall survival is 64.3% with a median
overall survival of 97.7 months compared to surgery alone with 44.2% with median OS of 41.0 months.

Conclusion

This study shows the feasibility and potential efficacy of the combination therapy of DCV and CD3-activated T cells transfer. Post-operative DCV resulted in improved RFS and OS in patients with HCC.

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Scientific article publishing date 1/13/2014

Immucura identifier BSC21_314EN

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