Palmer, Daniel H., Midgley, Rachel S., Mirza, Noweeda, Torr, Elizabeth E., Ahmed, Forhad, Steele, Jane C., Steven, Neil M., Kerr, David J., Young, Lawrence S. and Adams, David H. (2009) A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology, Vol.49 (No.1). pp. 124-132. doi:10.1002/hep.22626 ISSN 0270-9139.

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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 ≥3 months) was 28%. In 17 patients the baseline serum α-fetoprotein (AFP) was ≥ 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-γ (IFN-γ) 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.

Item Type:	Journal Article
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title:	Hepatology
Publisher:	John Wiley & Sons Inc
ISSN:	0270-9139
Official Date:	January 2009
Dates:	Date Event January 2009 Published
Volume:	Vol.49
Number:	No.1
Page Range:	pp. 124-132
DOI:	10.1002/hep.22626
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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