Poster Presentation Advances in Neuroblastoma Research Congress 2016
Anti-GD2 antibody combined with activated natural killer cells leads to improved survival and decreased metastasis in a minimal residual disease mouse model of neuroblastoma (#215)
Introduction: Relapsed metastatic disease is the primary cause of death for high-risk neuroblastoma patients following tumor resection. The FDA-approved anti-GD2 antibody (ch14.18) has been shown to improve survival in high-risk patients, and synergistic therapies are being sought. As previous studies demonstrated that natural killer (NK) cells augment the cytotoxicity of ch14.18 activity, we hypothesized that activated NK cells combined with ch14.18 would decrease metastasis and increase survival in a minimal residual disease mouse model of neuroblastoma.
Methods: 1x106 CHLA-255 neuroblastoma cells were intrarenally implanted into NSG mice, which were then randomized into 4 groups: control (n=5), ch14.18 (n=5), NK cell (n=6), NK cell+ch14.18 (n=6). Primary tumors were surgically resected on day 7, and mice were then treated 2x a week for 4 weeks. Incidence of liver and bone marrow metastasis was assessed by bioluminescent imaging. Survival was analyzed by Kaplan-Meier technique using log-rank test to determine significance. The incidence of metastasis was analyzed using Fisher’s exact test.
Results: At week 5, the NK cell+ch14.18 group had significantly less incidence of metastasis than the control and ch14.18 groups (1/6 vs 5/5 vs 5/5 liver, p=0.015; 0/6 vs 4/5 vs 4/5 femur, p=0.015). Survival in the NK cell+ch14.18 group was significantly increased compared to control (mean survival 52 vs 38 days, p=0.0157).
Conclusions: NK cells combined with ch14.18 following primary tumor resection significantly decreases incidence of metastasis and increases survival in NSG mice. This combination may serve as a valuable therapeutic option for the treatment of metastatic disease in children with high-risk neuroblastoma. 