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UNLABELLED: 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. CONCLUSION: 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.

Original publication

DOI

10.1002/hep.22626

Type

Journal article

Journal

Hepatology

Publication Date

01/2009

Volume

49

Pages

124 - 132

Keywords

Adolescent, Adult, Aged, Cancer Vaccines, Carcinoma, Hepatocellular, Cell Line, Tumor, Dendritic Cells, Female, Humans, Immunotherapy, Adoptive, Liver Neoplasms, Male, Middle Aged, Survival Analysis, Vaccination, alpha-Fetoproteins