IL-15 诱导的淋巴细胞作为胃癌辅助细胞免疫治疗

Objectives To test the antitumor potential of lymphocytes transferred via adoptive cell therapy (ACT) in a mouse model of human gastric cancer (GC), and to evaluate the clinical efficacy and safety of combining lymphocytes as adjuvant therapy with first-line chemotherapy in patients with GC.

Methods We constructed a human GC xenograft model in sublethally irradiated 6-8-week-old male NCG mice. MKN-45 cells (1 × 10 6 cells/mouse) were subcutaneously injected into mice's flanks. After tumors had become palpable, we randomized the mice into control, ACT IL-2 , and ACT IL-15 groups. Human lymphocytes were then injected into mouse tail veins.

In addition, 63 human patients with histologically or cytologically confirmed stage III-IV GC randomly received S-1 + oxaliplatin + ACT IL-15 (combination therapy group) or S-1 + oxaliplatin (chemotherapy group). Results In the mouse study, treatment with ACT IL-15 cells inhibited tumor growth on adoptive transfer, and mice that received ACT IL-15 cells had significantly longer survival rates (p < 0. 05, ACT IL-15 vs. ACT IL-2 ).

In the human study, the median survival rate of patients in the combination therapy group was 472 days (95% confidence interval [CI], 276-668 days), whereas that 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 these reactions did not interfere with treatment. Conclusion Adoptive transfer of ACT IL-15 cells in a mouse model of GC and in patients with advanced GC treated with S1 + oxaliplatin improved survival rates in both, with an acceptable safety profile.