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Title: Development of a dendritic cell-based vaccine for the immunotherapy of Acute Myeloid Leukaemia
Author: Klammer, Matthias
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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22 patients with de novo or relapsed Acute Myeloid Leukaemia (AML) were recruited into a Phase I/II clinical trial aimed at vaccinating with autologous dendritic like leukaemia cells once in complete remission. At trial entry leukaemia cells were harvested and tested for their permissiveness to cytokine-induced dendritic cell differentiation. Study patients were then treated with induction chemotherapy. Five patients achieved both complete remission and had leukaemia cells that were permissive to differentiation, and were therefore eligible to proceed to vaccination. Four escalating doses of dendritic like leukaemia cells were administered weekly by subcutaneous injection. An increase in anti-leukaemic T cell responses was demonstrated in four patients. Vaccination was generally well tolerated. Two patients relapsed during or shortly after the vaccination schedule. In the remaining three patients, one relapsed at 12 months with two in continued remission more than 12 months post vaccination. In a parallel investigation, the potential of Tumour Cell / Dendritic Cell Fusion Hybrids to generate in vitro anti-leukaemic T-cell responses following co-culture with autologous remission lymphocytes was assessed in six patients with AML. Comparison was made to anti-leukaemic responses induced by mature dendritic cells (mDC) co-cultured with autologous, irradiated myeloid blasts. Fusion Hybrids induced anti-leukaemic T-cell responses in three out of six patients. Tumour pulsed mature dendritic cells induced T-cellular responses in two other patients. Only one of six patient’s remission lymphocytes failed to develop leukaemia directed immune responses following stimulation with either construct. Anti-proliferative properties of Fusion Hybrids against allergenic lymphocytes were observed in mixed lymphocyte-leukaemia reactions (MLLR) and were found not to be specific to the cell fusion partners and do not prevent the ability of AML-mDC heterokaryons to induce autologous anti-leukaemic cytotoxicity. In conclusion, Tumour Cell / Dendritic Cell Fusion Hybrids hold promise as a cellular vaccine for Acute Myeloid Leukaemia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available