Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: UNIPROT:P06126 (
CD1a
)
2,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We report a method to generate dendritic cells (DC) from frozen leukapheresis products of patients with chronic myeloid leukemia (CML), using sterile culture bags and serum-free culture medium, ie conditions feasible for re-infusion into the patient as part of immunotherapeutic protocols. Leukapheresis products were stored from harvests performed either at diagnosis (13 patients) or after chemotherapy with subsequent
granulocyte colony stimulating factor
(
G-CSF
) administration (9 patients), for Peripheral Blood Stem Cell (PBSC) collections. In the presence of optimal concentrations of GM-CSF (50 ng/ml) and IL-4 (40 ng/ml) CML progenitors differentiated on day 7 and 14 of culture to DC, expressing
CD1a
,HLA-DR and CD86 surface antigens. Mature DCs exhibited on average 12-fold higher allo-stimulatory capacity for CD4+ and CD8+ cells compared to non-cultured PBMC in mixed lymphocyte reaction (MLR). Only DCs obtained from CML patients at diagnosis exhibited bcr/abl fusion gene when tested by fluorescent in situ hybridization (FISH). CD34-selection on leukapheresis products from diagnosis (7 patients) resulted in later maturation of DCs (after 14-15 d), compared to the nonselected PBMC. CD34-selection significantly increased the DC growth, and improved the allo-stimulatory capacity in MLR (on average on day 14, 3.5- and 2.3-fold, respectively). Large differences were observed between individual patients and different leukapheresis products from the same patient. Our report demonstrates the possibility to generate ex vivo autologous functionally active DC in CML in a way that allows their clinical application as immunotherapeutic agents.
...
PMID:Generation of dendritic cells from peripheral blood of patients at different stages of chronic myeloid leukemia. 1111 5
Dendritic cells (DC) are potent antigen-presenting cells that can induce effective tumour-specific T-cell responses. This study investigated leucapheresis products as source of DC precursors in 48 patients undergoing autologous peripheral blood stem cell (PBSC) transplantation for haematological malignancies. Strikingly, high-dose cytarabine and etoposide plus
granulocyte colony stimulating factor
(
G-CSF
) mobilized PBSC harvests from acute myeloid leukaemia (AML) patients containing the highest number of myeloid lin(neg)CD11c(pos) DC (mean: 7.04 x 106/kg, range: 1.46-19.67) which was 18.1-fold higher than in non-AML patients mobilized using chemotherapy (CT) regimens plus
G-CSF
. Clonality of purified lin(neg)CD11c(pos) DC from CT plus
G-CSF
mobilized AML patients (n = 8 ) was assessed using the human androgen-receptor locus methylation, disclosing a polyclonal pattern in five female patients. These cells displayed morphological and phenotypic features of myeloid DC precursors with expression of HLA-DR, HLA-ABC, CD86, CCR5 and CD54 molecules but lacking CD80, CD83,
CD1a
and CD40 antigens. Short-term culture with autologous leukaemic cell lysates plus tumour necrosis factor-alpha yielded maturated myeloid DC capable of triggering interleukin-2 and interferon-gamma production by autologous T-lymphocytes. These findings suggest that the use of post-remission CT and
G-CSF
as mobilizing regimen in AML patients generates PBSC containing high doses of polyclonal myeloid lin(neg)CD11c(pos) DC precursors, which could be used to design feasible immunotherapy protocols.
...
PMID:Chemotherapy plus G-CSF mobilized peripheral blood stem cell harvests from acute myeloid leukaemia patients contain large amounts of polyclonal myeloid linnegCD11cpos dendritic precursor cells. 1487 Dec 51