Vaccination of chronic myeloid leukemia patients with autologous in vitro cultured leukemic dendritic cells

CD40-targeted adenoviral GM-CSF gene transfer enhances and prolongs the maturation of human CML-derived dendritic cells upon cytokine deprivation

“…Although previous studies showed the ability of CML-DC to prime CML-specific cytotoxic T lymphocytes (CTL) in vitro (Choudhury et al, 1997;Eibl et al, 1997), we were unable to detect any CTL responses in a recently conducted clinical pilot study in which three IFN-aresistent CML patients in the late chronic phase of the disease were vaccinated with autologous, in vitro generated immature CML-DC (Ossenkoppele et al, 2003). In the same patients, we did observe postvaccination DTH responses against both CML Cytospins were prepared from CML cells and CML-DC and an interphase t(9;22) FISH was performed.…”

“…PBMC were isolated and CML-DC generated, phenotypically characterised, and tested for leukaemic origin by bcr-abl FISH, as previously described (Ossenkoppele et al, 2003).…”

“…It has become clear from clinical observations that chronic myeloid leukaemia (CML) is amenable to T-cell-mediated immune surveillance (Kolb et al, 1995). An immunotherapeutic approach may therefore provide a valuable adjuvant treatment option, especially in minimal residual disease settings.Leukaemic dendritic cells (DC), capable of eliciting T-cell responses against CML targets (Choudhury et al, 1997;Eibl et al, 1997), are easily generated, carry all possible tumour antigens, and can be used for autologous vaccination (Ossenkoppele et al, 2003). Although it is still unclear how long DC should maintain their mature phenotype and survive in vivo in order to generate an effective antitumour T-cell response, it is generally accepted that a stable mature DC phenotype is required to prevent reversion to a possibly tolerogenic immature precursor state subsequent to adoptive transfer.…”

TNF-α receptor 1 expression on acute myeloid leukemic blasts predicts differentiation into leukemic dendritic cells

“…1 In a recently performed phase-I study on CML-DC vaccination in advanced stage chronic myeloid leukemia (CML), we were able to detect strong DTH-responses representing autologous CML-specific T-cell responses. 2 The presence of various cytokines such as GM-CSF, SCF, Flt3-L, TNF-a, IL-3 and IL-4 induces differentiation into AML-DC in approximately 2 weeks, also under clinical grade serum-free The PIG3 polymorphic promoter shows LOH in de novo AML. Electropherograms obtained with labeled PCR products containing the PIG3 microsatellite (TGYCC)n. Top: sample obtained at diagnosis displayed a loss of the 17 repeats allelle (arrow).…”

“…After informed consent, peripheral blood and bone marrow mononuclear cells of AML patients were collected. A total of 33 patients (21 female, 12 male) were included with a median age of 60 years (range: 22-88), with the following FAB classifications: M0 (2), M1 (5), M2 (5), M4 (8), M5 (10), RAEB-t (1), unclassified (2). AML cells were cultured as published previously.…”