Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia.
In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by constitutive expression of bcr/abl and possibly other yet undefined leukemia-associated antigens, since these DC share a common progeny with leukemic cells. Induction of anti-leukemic T cell responses has been described in vitro. For a phase I vaccination study, autologous bcr/abl+ DC are generated under GMP conditions mainly from monocyte precursors in chronic phase CML patients. Lin-, CD80+, CD86+, CD83+, DR+ DC could be generated in sufficient numbers for s.c. vaccination with 1 x 10(6)-5 x 10(7) DC. Using monocyte precursors, the yield of DC per seeded PBMC was in the range of 1-6%. Furthermore, we could demonstrate in vitro that the T cell stimulatory ability of CD34+-derived DC can be augmented by a factor 2-3 by retroviral transduction with a gene coding for interleukin-7. DC-based vaccination strategies are a promising clinical approach, particularly as postremission immunotherapy in the setting of autologous stem cell transplantation.
Westermann
J
J
Dept of Hematology, Oncology and Tumorimmunology, Robert Rössle Klinik, Charité, Humboldt University, Berlin, Germany.
Kopp
J
J
Körner
I
I
Richter
G
G
Qin
Z
Z
Blankenstein
T
T
Dörken
B
B
Pezzutto
A
A
D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics; D015466:Leukemia, Myeloid, Chronic-Phase / Q000276:immunology / Q000628:therapy*; D009000:Monocytes / Q000276:immunology; D014161:Transduction, Genetic; D014182:Transplantation, Autologous; D014611:Vaccination
D015851:Interleukin-7; D016044:Fusion Proteins, bcr-abl