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.
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.