title: Enhancement of the cytotoxic activity of cytokine-induced killer cells transfected with IL3PE38KDEL gene against acute myeloid leukemia cells.
abstract: Cytokine-induced killer (CIK) cells, one of the feasible and effective methods of adoptive immunotherapy, have shown anti-leukemia activity in vivo and in vitro. But the strategy exhibits limited cytotoxic activity in clinical studies. In this study, CIK cells were transfected with an interleukin-3/Pseudomonas exotoxin gene (IL3PE38KDEL). RT-PCR and ELISA were used to verify the expression of IL3PE38KDEL in the transfected CIK cells. These cells released 1,186.7 ± 149.6 pg IL3PE38KDEL/10(4) cells over 48 h into the medium and the culture supernatant selectively killed IL3 receptor(IL3R)-positive HL60 cells, but not IL3R-negative K562 cells. Moreover, IL3PE38KDEL transfection did not influence phenotypes and cytokine production of CIK cells. Co-cultured with leukemia cells, IL3PE38KDEL transfected CIK cells showed enhanced cytotoxicity against IL3R-positive HL60 cells at all effector-to-target (E:T) ratios, but exerted a basal anti-leukemia activity against IL3R-negative K562 cells. Our findings demonstrate that IL3PE38KDEL gene transfection may be a novel strategy for improving anti-leukemia activity of CIK cells.
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Chongqing Medical University, Linjiang Road 76, Chongqing, 400010, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: FengXia
authors.initials: F
authors.lastname: Bai
authors.forename: ShiDi
authors.initials: S
authors.lastname: Cheng
authors.forename: ShiFeng
authors.initials: S
authors.lastname: Lou
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics; D018920:Coculture Techniques; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005098:Exotoxins / Q000235:genetics / Q000502:physiology*; D005813:Genes, Synthetic; D018922:HL-60 Cells; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007371:Interferon-gamma / Q000032:analysis; D007377:Interleukin-3 / Q000235:genetics / Q000502:physiology*; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009154:Mutation; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000235:genetics*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D007371:Interferon-gamma; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C573415:IFNG protein, human