Abstract
To test the antitumor potential of adoptive cell therapy (ACT)-transferred lymphocytes in a mouse model of human gastric cancer, and evaluate the clinical efficacy and safety of combining lymphocytes as adjuvant therapy with first-line chemotherapy in patients with gastric cancer. A human gastric cancer xenograft model was constructed in sublethally irradiated 6–8-week old NCG male mice. MKN-45 cells (1 × 106 cells/mouse) were subcutaneously injected into the flanks. After tumors had become palpable, the mice were randomized into control, ACTIL-2, and ACTIL-15 groups. Human lymphocytes were injected into the mouse tail veins. In addition, 63 patients who had histological or cytologically confirmed stage III–IV gastric cancer randomly received S-1 plus oxaliplatin plus ACTIL-15 (a combination therapy group) or S-1 plus oxaliplatin alone (chemotherapy group). In the mice, treatment with ACTIL-15 cells inhibited tumor growth upon adoptive transfer, and mice that received ACTIL-15 cells had a significantly longer survival (P < 0.05, ACTIL-15 vs. ACTIL-2). In the human study, the median survival of patients in the combination therapy group was 472 days (95% confidence interval (CI), 276–668 days), whereas the median survival of patients in the chemotherapy group was 266 days (95% CI, 200–332 days; P < 0.05). Eleven percent (7/63) of patients had adverse reactions, but the reactions did not interfere with treatment. Adoptive transfer of ACTIL-15 cells in a mouse model of gastric cancer and patients with advanced gastric cancer treated with S1 and oxaliplatin improved survival with an acceptable safety profile.
Anti-metastatic Efficacy of Traditional Chinese Medicine (TCM) Ginsenoside Conjugated to a VEFGR-3 Antibody on Human Gastric Cancer in an Orthotopic Mouse Model
