title: 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: OBJECTIVE
  Hepatocellular 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.
  
  
  METHODS
  Previously 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.
  
  
  RESULTS
  HCC 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.
  
  
  CONCLUSIONS
  Autologous DC-TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned.
authors: Hospital 85 People's Liberation Army of China, Shanghai, China.
authors: Xiaojin
authors: X
authors: Wang
authors: Michael E
authors: ME
authors: Bayer
authors: Xiaosong
authors: X
authors: Chen
authors: Craig
authors: C
authors: Fredrickson
authors: Andrew N
authors: AN
authors: Cornforth
authors: Greg
authors: G
authors: Liang
authors: Jessica
authors: J
authors: Cannon
authors: Jia
authors: J
authors: He
authors: Qingchun
authors: Q
authors: Fu
authors: Jia
authors: J
authors: Liu
authors: Gabriel I
authors: GI
authors: Nistor
authors: Wei
authors: W
authors: Cao
authors: Chengwei
authors: C
authors: Chen
authors: Robert O
authors: RO
authors: Dillman
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy* / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000637:transplantation*; D011379:Prognosis; D014182:Transplantation, Autologous
keywords: dendritic cell vaccine; hepatitis B; hepatocellular carcinoma; therapeutic cancer vaccines; tumor stem cells