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

Abstract

Background and ObjectivesHepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long‐term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high‐risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis.MethodsPreviously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC‐TC. After one course of trans‐arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC‐TC suspended in granulocyte‐macrophage colony stimulating factor were administered. Patients were monitored for eight weeks.ResultsHCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA.ConclusionAutologous DC‐TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. J. Surg. Oncol. 2015 111:862–867. © 2014 Wiley Periodicals, Inc.