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Nonleukemic myeloid dendritic cells obtained from autologous stem cell products elicit antileukemia responses in patients with acute myeloid leukemia
Author(s) -
SerranoLópez Juana,
SanchezGarcia Joaquin,
Serrano Josefina,
AlvarezRivas Miguel A.,
GarciaCastellano Jose M.,
RomanGomez Jose,
Rosa Olga de la,
HerreraArroyo Concepcion,
TorresGomez Antonio
Publication year - 2011
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2010.03042.x
Subject(s) - myeloid leukemia , ex vivo , leukemia , myeloid , dendritic cell , immunology , stem cell , transplantation , medicine , immunotherapy , cancer research , biology , immune system , in vivo , genetics , microbiology and biotechnology
BACKGROUND: Dendritic cell (DC)‐based immunotherapeutic protocols are being developed to treat acute myeloid leukemia (AML). So far, DCs for clinical use are obtained from leukemic blasts or from monocytes, after 6 to 10 days of ex vivo culture. However, DC precursors are easily driven to DCs in short‐term culture. We tested if DC precursors contained in peripheral blood stem cell (PBSC) products obtained from AML patients can be used to induce antileukemia responses. STUDY DESIGN AND METHODS: PBSCs obtained from 30 consecutive AML patients were tested. Myeloid DCs (MDCs) were purified by immunomagnetic selection and screened for cytogenetic and/or molecular abnormalities by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) assays. MDCs were matured and pulsed with autologous blast lysates and tested for stimulatory capability against AML cells. RESULTS: A median of 0.62 × 10 6 MDCs (range, 0.04‐3.25)/mL were quantified in PBSC products. Isolated MDC expressed Class I and II HLA but CD86, CD54, and CCR5 partially. By FISH or PCR assay, these MDCs lacked cytogenetic or molecular abnormalities detected in leukemia cells at diagnosis. MDCs achieved a maturated stage (mature‐MDCs) after 24‐hour ex vivo culture with tumor necrosis factor‐α and autologous blast lysates. These mature‐MDCs were capable of stimulating autologous peripheral blood effectors to exert cytotoxicity against autologous leukemia cells and HL‐60 cell line. CONCLUSION: We conclude that PBSCs obtained for autologous stem cell transplantation can constitute a novel source of MDCs to design feasible vaccination trials.