P0976 - Neoadjuvant Immunotherapy with Activated Natural Killer Cells and anti-GD2 Antibody Dinutuximab Before Resection of Primary Neuroblastoma Prolongs Survival

Purpose:
Following induction chemotherapy, surgery, and myeloablative chemotherapy, immunotherapy with anti-disialoganglioside (GD2) antibody (dinutuximab) improves survival for children with high-risk neuroblastoma, but progressive disease still develops in approximately 50% of patients. However, the survival benefit of neoadjuvant immunotherapy prior to tumor resection has not been evaluated. Using a mouse model of neuroblastoma, we hypothesized that initiating immunotherapy prior to tumor resection improves survival.

Methods:
Three human neuroblastoma cell lines (CHLA-255-Fluc, SMS-KCNR-Fluc, or PDX COG-N-415x) were intra-renally implanted in immunodeficient NOD-scid gamma mice (n=35 mice per cell line). Mice underwent resection of xenografted tumors on day 19 and received intravenous aNK cells and dinutuximab twice weekly for 4 weeks beginning either 12 days before (“early immunotherapy”) or 2 days after (“late immunotherapy”) surgery; control mice underwent resection only or received immunotherapy without resection. Total disease burden was quantified with weekly bioluminescent imaging. Survival was measured from the day of tumor cell injection, to a maximum of 100 days. Area under the curve was calculated for bioluminescent data and log transformed. Linear regression was used to analyze differences in bioluminescent and survival data between treatment groups. P-value < 0.05 was considered significant.

Results:
Mice treated with aNK cells plus dinutuximab prior to tumor resection had significantly less disease burden compared to mice treated after resection. Neoadjuvant treatment with aNK cells plus dinutuximab significantly increased survival compared to adjuvant immunotherapy following surgery. (Figure 1)

Conclusion:
Immunotherapy with dinutuximab plus adoptively transferred aNK cells initiated before resection of the primary tumor significantly decreases metastatic disease burden and prolongs survival compared to standard immunotherapy following surgical resection. Neoadjuvant immunotherapy with dinutuximab plus aNK cells may improve the efficacy of immunotherapy in patients with high-risk neuroblastoma.