Header menu link for other important links
X
CD25 targeted therapy of chemotherapy resistant leukemic stem cells using DR5 specific TRAIL peptide
Published in Elsevier B.V.
2017
PMID: 28076753
Volume: 19
   
Pages: 65 - 75
Abstract

Chemotherapy resistant leukemic stem cells (LSCs) are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP) of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81.25% in AML and 100% in CML, ALL and CLL. IL2-TRAIL peptide showed cytotoxicity in relapsed patient samples and was more effective than TRAIL or IL2-TRAIL proteins. Additionally, DR5 specific IL2-TRAIL peptide was effective in targeting and killing LSCs purified from cell lines [IC50: 952 nM in HL60, 714 nM in MOLT4] and relapsed patient blood samples with higher efficacy (85%) than IL2-TRAIL protein (46%). Hence, CD25 and DR5 specific targeting by IL2-TRAIL peptide may be an effective strategy for targeting drug resistant leukemic cells and LSCs. © 2017

About the journal
JournalData powered by TypesetStem Cell Research
PublisherData powered by TypesetElsevier B.V.
ISSN18735061
Open AccessYes
Concepts (63)
  •  related image
    DEATH RECEPTOR 5
  •  related image
    IMMUNOTOXIN
  •  related image
    INTERLEUKIN 2 RECEPTOR ALPHA
  •  related image
    Methotrexate
  •  related image
    TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND
  •  related image
    IMMUNOTOXIN
  •  related image
    INTERLEUKIN 2
  •  related image
    INTERLEUKIN 2 RECEPTOR ALPHA
  •  related image
    Peptide
  •  related image
    TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND
  •  related image
    TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND RECEPTOR
  •  related image
    Apoptosis
  •  related image
    Article
  •  related image
    Blood sampling
  •  related image
    Cancer chemotherapy
  •  related image
    Cell population
  •  related image
    Cell proliferation
  •  related image
    Cell viability
  •  related image
    Controlled study
  •  related image
    Drug conjugation
  •  related image
    Drug cytotoxicity
  •  related image
    Flow cytometry
  •  related image
    FLUORESCENCE ACTIVATED CELL SORTING
  •  related image
    Fluorescence microscopy
  •  related image
    Human
  •  related image
    Human cell
  •  related image
    Leukemia cell
  •  related image
    Membrane potential
  •  related image
    PERIPHERAL BLOOD MONONUCLEAR CELL
  •  related image
    Priority journal
  •  related image
    Real time polymerase chain reaction
  •  related image
    Stem cell
  •  related image
    Western blotting
  •  related image
    Antagonists and inhibitors
  •  related image
    CANCER STEM CELL
  •  related image
    Cell cycle checkpoint
  •  related image
    Chemistry
  •  related image
    Cytology
  •  related image
    Drug effects
  •  related image
    Drug resistance
  •  related image
    Genetics
  •  related image
    HL-60 CELL LINE
  •  related image
    Leukemia
  •  related image
    Metabolism
  •  related image
    Mononuclear cell
  •  related image
    Pathology
  •  related image
    RECURRENT DISEASE
  •  related image
    Tumor cell line
  •  related image
    Cell cycle checkpoints
  •  related image
    Cell line, tumor
  •  related image
    Drug resistance, neoplasm
  •  related image
    HL-60 CELLS
  •  related image
    Humans
  •  related image
    IMMUNOTOXINS
  •  related image
    INTERLEUKIN-2
  •  related image
    INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT
  •  related image
    LEUKOCYTES, MONONUCLEAR
  •  related image
    Microscopy, fluorescence
  •  related image
    NEOPLASTIC STEM CELLS
  •  related image
    Peptides
  •  related image
    RECEPTORS, TNF-RELATED APOPTOSIS-INDUCING LIGAND
  •  related image
    RECURRENCE
  •  related image
    TNF-RELATED APOPTOSIS-INDUCING LIGAND