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Dendritic Cell Immunotherapy of Hepatitis C Virus Infection: Toxicology of Lipopeptide-Loaded Dendritic Cells

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Abstract

Before carrying out a clinical trial in humans in which a cell-based therapeutic anti-hepatitis C virus lipopeptide vaccine candidate is to be evaluated, a limited toxicological study was carried out. Murine bone marrow-derived dendritic cells (DCs) were loaded with lipopeptides containing HLA A2.1-restricted epitopes recognised by cytotoxic T lymphocytes (CTL) and then injected into C57BL6 mice by intradermal and intravenous routes. No significant behavioural changes, clinical symptoms or changes in body weight were observed when compared with a control group of animals receiving no treatment. One week after the third dose of lipopeptide-pulsed DC, mice were killed and blood samples taken for biochemical and hematological analyses. The liver, spleen and skin at the injection site were also collected and processed for histological analysis. Mild eosinophilia was observed at intradermal injection sites of animals receiving untreated as well as lipopeptide-loaded DCs. Despite a slight decrease in the size of livers of animals receiving lipopeptide-pulsed DCs, there was no evidence of inflammatory infiltrate or histological change. The only biochemical or hematological abnormality associated with the injection of lipopeptide-pulsed DC was a slight reduction in potassium levels. The evidence indicates that the lipopeptide vaccines per se are not cytotoxic and do not induce adverse events. On this basis, the TGA has granted clinical trial by exemption (CTX) approval for the proposed study using HCV lipopeptide-pulsed autologous DC to proceed in humans. This is the first approval of its kind in Australia setting a precedent for somatic cell immunotherapy of infectious disease.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia

    David C. Jackson & Emily Eriksson

  2. VaxTX Pty Ltd., Level 1, 123 Camberwell Road, 3123, East Hawthorn, VIC, Australia

    Georgia Deliyannis, Irene Dinatale & Michael Rizkalla

  3. Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, 3001, Melbourne, VIC, Australia

    Eric J. Gowans

Authors
  1. David C. Jackson
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  2. Georgia Deliyannis
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  3. Emily Eriksson
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  4. Irene Dinatale
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  5. Michael Rizkalla
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  6. Eric J. Gowans
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Correspondence to David C. Jackson.

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Jackson, D.C., Deliyannis, G., Eriksson, E. et al. Dendritic Cell Immunotherapy of Hepatitis C Virus Infection: Toxicology of Lipopeptide-Loaded Dendritic Cells. Int J Pept Res Ther 11, 223–235 (2005). https://doi.org/10.1007/s10989-005-9270-y

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  • DOI: https://doi.org/10.1007/s10989-005-9270-y

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