Phase I/II study of Immunotherapy using Tumor Antigen-pulsed Dendritic Cells in patients with Hepatocellular Carcinoma (HCC)
Clinical response to DC vaccine
Summary
This study evaluated the safety, feasibility and efficacy of multiple tumor-associated antigen (TAA)-pulsed DC vaccine in patients with hepatocellular carcinoma. The feasibility, safety and immune activity were confirmed in the patients.
Patients characteristics
5 Patients with hepatocellular stage II and III ages 46-64 years old with previous treatment with Transcatheter hepatic arterial chemoembolization (TACE).
Methodology
• Monocytes were obtained from HCC patients through leukapheresis, PBMCs were separated from WBC by Ficoll-Hypaque density gradient centrifugation.
• PBMCs thawed, washed with Hanks Balanced Salt solution, resuspended in RPMI-1640 medium, supplemented with autologous heat-inactivated plasma and then incubated in culture chambers.
• After 0.5-1 hour incubation at 37C in 5% CO2 incubation, non- adherent cells were removed by gentle washes.
• Adherent cells were cultured with X-VIVO15 supplemented with GM- CSF, IL-4 for 5 days.
• On day 5, non-attached iDC were harvested and pulsed with CTP- fused human AFP, MAGE1 and GPC-3 recombinant proteins at a final concentration of 5 ng/mL each.
• Antigen pulsed DC were matured in the presence of cytokine cocktail, IL-6, IL-1B, TNF-a, prostaglandin E2, IFN-y, OK432 and poly I:C for 1 or 2 days.
• On day 6-7, DC were harvested, washed and resuspended in 1.2mL of cryopreserving solution containing 5% dimethyl sulfoxide.
Treatment
DC vaccine was administered subcutaneously (SC) near inguinal lymph node.
Results
• Toxicity was mild and no grade III/IV serious adverse events.
• No hematological, hepatic or renal toxicity or de novo autoantibody
formation were observed in any of the 5 patients.
• Clinical response achieved in 1 patient with disease stabilization during the follow-up period, however, no tumor response was observed in other 4 patients.
• All 5 patients showed T cell responses against TAAs.
Conclusion
DC vaccine was safe and well tolerated over 6 vaccines in 5 patients. The feasibility, safety and immune activity of DC pulsed with TAAs were confirmed in HCC patients. However clinical response was only detected in 1 patient.