title: Augmented CD3(+)CD8(+) and CD3(+)CD56(-) cells in cytokine-induced killer cells cultured with engineered cells for costimulatory enhancement from heavily pretreated patients with solid tumor.
abstract: OBJECTIVE
  Cytokine-induced killer cells (CIKs) were shown to be a promising tool in the quest for new therapeutic approaches in the setting of metastatic solid tumors refractory to standard treatments. However, there is a practical clinical problem of different expansion rates and cell function as individual variability exists. Stimulatory molecular 4-1BB could promote division and survival of T cells and enhance effector activity including cytokine production. This study aimed to invest the contribution of co-stimulation signal to CIKs production for exploring new strategies, which increase the expansion and reliability of CIKs generation to improve access to CIKs therapy.
  
  
  METHODS
  We studied the larger-scale expansion of CIKs cultured with engineered cells for costimulatory enhancement (ECCE) consisting of K562 cells that expressed 4-1BBL in heavily pretreated patients with solid tumor. The proliferation and cytotoxic capacity of CIKs were evaluated. Phenotypes of CIKs were analyzed using flow cytometry. Cytokine levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected using enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The proliferation and cytotoxic activity of CIKs were significantly up-regulated by ECCE. The percentages of CD3(+)CD8(+) and CD3(+)CD56(-) CIKs were significantly increased while the percentage of CD3(+)CD56(+) CIKs was decreased. In addition, the secretion of IFN-γ and TNF-α by CIKs could also be enhanced significantly when ECCE were added into the culture system.
  
  
  CONCLUSIONS
  This study suggests that ECCE may improve the efficacy of CIKs therapy and make CIKs therapy possible for the patients whose CIKs would be hard to be cultured using conventional methods.
authors.affiliation: Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China; Surgical Department, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yin
authors.affiliation: Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China.
authors.forename: Zhenxian
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China; Liver Disease Department, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China. Electronic address: yeweiseu@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China; Liver Disease Department, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, China. Electronic address: zhaowei195612@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D060846:Cell Engineering / Q000379:methods*; D002478:Cells, Cultured; D055612:Cytokine-Induced Killer Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D016879:Salvage Therapy / Q000379:methods
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D016827:CD8 Antigens
keywords: 4-1BBL; adoptive T-cell immunotherapy; co-stimulation; cytokine-induced killer cells