Abstract:
:It has been proposed that adoptive immunotherapy, for the treatment of relapsed AML, with cytotoxic T lymphocytes which show a relative specificity for the leukemic cells may have the advantage of maximizing the beneficial anti-leukemic effect whilst minimizing the probability of graft-versus-host disease. In this study we differentiated peripheral blood AML cells in vitro into functional dendritic cells (DCs), as demonstrated by cell morphology, immunophenotype and functional activity, in the presence of GM-CSF, IL-4, TNF-alpha and FLT3 ligand. Such DCs could be differentiated from 77% of AML patients, irrespective of their FAB classification and clinical status and, in all cases tested, the DCs were shown to derive from the leukemic clone by FISH analysis. Importantly, from >60% of AML patients, autologous T lymphocytes stimulated with these in vitro generated leukemic DCs displayed specific cytotoxic activity against AML blasts but low reactivity against autologous non-leukemic targets and HLA-matched normal PBMNCs therefore suggesting that the CTLs were AML-specific. The use of FLT3 ligand in our system resulted in a significantly higher number of leukemic DCs as compared to cultures from which FLT3 ligand was omitted which is obviously advantageous if large numbers of specific CTLs are to be generated in the shortest possible time.
journal_name
Leukemiajournal_title
Leukemiaauthors
Woiciechowsky A,Regn S,Kolb HJ,Roskrow Mdoi
10.1038/sj.leu.2402013subject
Has Abstractpub_date
2001-02-01 00:00:00pages
246-55issue
2eissn
0887-6924issn
1476-5551journal_volume
15pub_type
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