title: Synergistic effect of CH-296 and interferon gamma on cytokine-induced killer cells expansion for patients with advanced-stage malignant solid tumors.
abstract: BACKGROUND
  Cytokine-induced killer cells (CIKs) are heterogenous antitumor effectors including interferon gamma (IFN-γ)-amplified CD3(+)CD56(+) cells. CH-296 has been shown to stimulate T-cell proliferation in the presence of T cell receptor (TCR)-stimulating signals. The purpose of this study was to investigate the synergistic effect of CH-296 and IFN-γ on expansion of CIKs for treating patients with advanced-stage malignant solid tumors.
  
  
  METHODS
  CIKs were cultured with immobilized CH-296 in the presence (retronectin [RN]-CIKs) or absence of IFN-γ (RN-CIKs/del) for 14 days. Proliferation, apoptosis, phenotype, and cytotoxicity were detected. Twenty (20) patients (18 patients with stage IV solid tumors) received three cycles of RN-CIKs treatment. The clinical responses were evaluated using Karnofsky Performance Status scoring and computed-tomography scanning.
  
  
  RESULTS
  CH-296 promoted CIKs expansion in a time-dependent manner by inhibiting apoptosis and increasing proliferation. Costimulation of CH-296 and IFN-γ amplified more antitumor effectors of CIKs with activated T-cell phenotype, which displayed potent cytotoxicity and increased cytokines secretion upon antigen priming. Sixteen (16) patients receiving RN-CIKs experienced relief of clinical symptoms. The overall clinical response rate was 65% (13/20) and the mean overall survival was 16.95±6.10 months. No severe adverse events were observed in the clinical trial.
  
  
  CONCLUSIONS
  CH-296 and IFN-γ synergistically promote antitumor efficiency of CIKs by increasing proliferation, inhibiting apoptosis, and enhancing cytotoxicity.
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tiyuanbei, Huanhuxi Road, Hexi District, Tianjin, China.
authors.forename: Jinpu
authors.initials: J
authors.lastname: Yu
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Shui
authors.initials: S
authors.lastname: Cao
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Enoki
authors.forename: Ikunoshin
authors.initials: I
authors.lastname: Kato
authors.forename: Chunyu
authors.initials: C
authors.lastname: Cao
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005353:Fibronectins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005353:Fibronectins; D011994:Recombinant Proteins; C545354:retronectin; D007371:Interferon-gamma