Enhancement of the cytotoxic activity of cytokine-induced killer cells transfected with IL3PE38KDEL gene against acute myeloid leukemia cells

• Published in: Annals of hematology Vol. 93; no. 12; pp. 2019 - 2028
• Main Authors: Shen, Yan, Liu, Qi, Luo, Yun, Zhang, Ping, Bai, FengXia, Cheng, ShiDi, Lou, ShiFeng
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2014; Springer Nature B.V
• Subjects: ADP Ribose Transferases - genetics; ADP Ribose Transferases - physiology; Bacterial Toxins - genetics; Coculture Techniques; Cytokine-Induced Killer Cells - immunology; Cytotoxicity, Immunologic; Exotoxins - genetics; Exotoxins - physiology; Genes, Synthetic; Hematology; HL-60 Cells; Humans; Immunophenotyping; Immunotherapy; Interferon-gamma - analysis; Interleukin-3 - genetics; Interleukin-3 - physiology; K562 Cells; Leukemia, Myeloid, Acute - pathology; Medicine; Medicine & Public Health; Mutation; Oncology; Original Article; Protein Structure, Tertiary; Pseudomonas; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa Exotoxin A; Transfection; Tumor Necrosis Factor-alpha - analysis; Virulence Factors - genetics; Virulence Factors - physiology; IL3PE38KDEL; Cytotoxicity; Immunotoxin; Cytokine-induced killer cells; Acute myeloid leukemia
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-014-2146-5

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.