Vaccination with autologous non-irradiated dendritic cells in patients with bcr/abl+ chronic myeloid leukaemia.
In chronic myeloid leukaemia (CML), dendritic cells (DC) and leukaemic cells share a common progeny, leading to constitutive expression of putative tumour antigens, such as bcr/abl, in DC. In this phase-I/II study, autologous DC were used as a vaccine in patients with chronic phase bcr/abl+ CML, who had not achieved an adequate cytogenetic response after treatment with alpha-interferon or imatinib. Ten patients were enrolled, DC were generated from peripheral blood monocytes and vaccination consisted of four subcutaneous injections of increasing numbers of DC (1-50 x 10(6) cells per injection) on days 1, 2, 8 and 21. Vaccination was feasible and safe. Improvement of the cytogenetic/molecular response, as detected by fluorescence in situ hybridization of peripheral blood mononuclear cells (PBMC), was possibly related to vaccination in four of 10 patients. In three of these patients, T cells recognizing leukaemia-associated antigens became detectable. The proliferative capacity of PBMC in response to autologous DC increased after vaccination in all evaluable patients. We conclude that vaccination with autologous, non-irradiated 'leukaemic' DC is feasible, safe and induces anti-leukaemic T-cell responses in some CML patients. DC vaccination might be useful in CML as postremission therapy, i.e. after treatment with tyrosine kinase inhibitors.
Westermann
Jörg
J
Department of Haematology and Oncology, Charité, University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany. joerg.westermann@charite.de
Kopp
Joachim
J
van Lessen
Antje
A
Hecker
Ann-Christine
AC
Baskaynak
Gökben
G
le Coutre
Philipp
P
Döhner
Konstanze
K
Döhner
Hartmut
H
Dörken
Bernd
B
Pezzutto
Antonio
A
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology; D049109:Cell Proliferation; D003582:Cytogenetics; D003713:Dendritic Cells / Q000637:transplantation*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D016219:Immunotherapy, Adoptive; D017404:In Situ Hybridization, Fluorescence; D007371:Interferon-gamma / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D000951:Antigens, Neoplasm; D007371:Interferon-gamma; D016044:Fusion Proteins, bcr-abl