Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B positive patients with hepatocellular carcinoma

Background Active or chronic infections may be barriers to successful vaccines, and patients with hepatitis typically are excluded from clinical trials testing therapeutic anticancer vaccines. One concern is vaccines may exacerbate the underlying infection. Hepatocellular carcinoma (HCC) often arises in the context of viral hepatitis B (HBV) or hepatitis C (HBC), with or without cirrhosis. HCC is seldom cured by standard therapy because of undetectable micrometastatic disease that is present at diagnosis. Effective nontoxic adjunctive treatments might improve outcomes for HCC patients who are at high risk for recurrence and death despite surgical resection of their primary hepatoma. Active specific immunotherapy (ASI) with autologous dendritic cells loaded with antigens from autologous tumor stem cell lines has been associated with promising long-term survival in metastatic melanoma, but patients with HBV or HCV were ineligible. Therefore a Phase I safety trial in HCC patients with HBV and/or HIV was warranted. Patients and methods Patients with previously untreated HCC who were candidates for surgical resection, but not curable by resection or liver transplant were enrolled in Shanghai, China. Patients had a solitary lesion >5 cm in diameter, or 3 lesions with at least one > 3 cm, but no regional or distant metastatic disease. Patients had a good performance status, adequate blood counts and organ function. An autologous tumor cell (TC) line was established from the resected tumor. Irradiated autologous TC were incubated with autologous dendritic cells (DC) to create a patient-specific DC-TC product which was cryopreserved. Approximately eight weeks after one course of transarterial chemoembolization therapy (TACE), patients received three weekly subcutaneous injections of DC-TC suspended in 500 micrograms of sargramostim. Patients were monitored for toxicity for 8 weeks from the start of treatment.