These authors contributed equally to this work.
A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma†
Article first published online: 3 NOV 2008
Copyright © 2008 American Association for the Study of Liver Diseases
Volume 49, Issue 1, pages 124–132, January 2009
How to Cite
Palmer, D. H., Midgley, R. S., Mirza, N., Torr, E. E., Ahmed, F., Steele, J. C., Steven, N. M., Kerr, D. J., Young, L. S. and Adams, D. H. (2009), A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology, 49: 124–132. doi: 10.1002/hep.22626
Potential conflict of interest: Nothing to report.
- Issue published online: 28 DEC 2008
- Article first published online: 3 NOV 2008
- Manuscript Accepted: 9 SEP 2008
- Manuscript Received: 1 JUL 2008
- Cancer Research UK
- Alan Morement Memorial Fund
- Cancer Research UK Clinician Scientist Fellowship
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. (HEPATOLOGY 2009;49:124-132.)