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.
Dendritic cells lipopeptide vaccines toxicology
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Fishman, J. A., Rubin, R. H., Koziel, M. J., Periera, B. J. 1996Transplantation62147154PubMedGoogle Scholar
Frese, M., Schwarzle, V., Barth, K., Krieger, N., Lohmann, V., Mihm, S., Haller, O., Bartenschlager, R. 2002Hepatology35694703CrossRefPubMedGoogle Scholar
Garcia, F., Lejeune, M., Climent, N., Gil, C., Alcami, J., Morente, V., Alos, L., Ruiz, A., Setoain, J., Fumero, E., Castro, P., Lopez, A., Cruceta, A., Piera, C., Florence, E., Pereira, A., Libois, A., Gonzalez, N., Guila, M., Caballero, M., Lomena, F., Joseph, J., Miro, J. M., Pumarola, T., Plana, M., Gatell, J. M., Gallart, T. 2005Therapeutic immunization with dendritic cells loaded with head – in activated autologous HIV-1 in patients with chronic HIV-1 infectionJ Infect Dis19116801685PubMedGoogle Scholar