title: A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma.
abstract: This is a phase II clinical trial investigating the safety and efficacy of intravenous vaccination with mature autologous dendritic cells (DCs) pulsed ex vivo with a liver tumor cell line lysate (HepG2) in patients with advanced hepatocellular carcinoma (HCC). HCC is an attractive target for immunotherapy as evidenced by an active recruitment of tumor-infiltrating lymphocytes that are capable of lysing autologous tumor cells in ex vivo studies. DCs are the most potent antigen-presenting cells, with the capacity to take up, process, and present tumor antigens to T cells and stimulate an immune response, thus providing a rational platform for vaccine development. Thirty-five patients with advanced HCC and not suitable for radical or loco-regional therapies received a maximum of six DC vaccinations each at 3-week intervals. In total, 134 DC infusions were administered with no significant toxicity and no evidence of autoimmunity. Twenty-five patients who received at least three vaccine infusions were assessed clinically for response. The radiologically determined disease control rate (combined partial response and stable disease >or=3 months) was 28%. In 17 patients the baseline serum alpha-fetoprotein (AFP) was >or= 1,000 ng/mL; in four of these patients, it fell to <30% of baseline following vaccination. In one patient there was a radiological partial response associated with a fall in AFP to <10% of baseline. Immune responses were assessed using an ELIspot assay of interferon-gamma (IFN-gamma) release. In several cases there was induction of T cell responses to the vaccine and/or AFP following vaccination.
  
  
  CONCLUSIONS
  Autologous DC vaccination in patients with HCC is safe and well tolerated with evidence of antitumor efficacy assessed radiologically and serologically, with generation of antigen-specific immune responses in some cases.
authors.affiliation: Cancer Research UK Clinical Trials Unit, CR UK Institute for Cancer Studies, Clinical Research Block. d.palmer@bham.ac.uk
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Palmer
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Midgley
authors.forename: Noweeda
authors.initials: N
authors.lastname: Mirza
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Torr
authors.forename: Forhad
authors.initials: F
authors.lastname: Ahmed
authors.forename: Jane C
authors.initials: JC
authors.lastname: Steele
authors.forename: Neil M
authors.initials: NM
authors.lastname: Steven
authors.forename: David J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Young
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014611:Vaccination; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D000509:alpha-Fetoproteins