ESPU Congress 2018 - Abstract Book

48 29 th CONGRESS OF THE ESPU 16:35–16:38 S3-14 (PP) ★ NEUROBLASTOMA CHEMOTHERAPY CAN BE AUGMENTED BY IMMUNOTARGETING O-ACETYL-GD2 TUMOR-ASSOCIATED GANGLIOSIDE Sebastien FARAJ  1 , Meriem BAHRI  2 , Sophie FOUGERAY  2 , Estelle THEBAUD  3 , Marc David LECLAIR  1 , Francois PARIS  2 and Stephane BIRKLE  2 1) CHU Nantes, Pediatric Surgery, Nantes, FRANCE - 2) CRCINA, UMR Inserm U892-CNRS 6299, Nantes, FRANCE - 3) CHU Nantes, Pediatric Oncology, Nantes, FRANCE PURPOSE Despite recent advances in high-risk neuroblastoma therapy, the prognosis for patients remains poor. In addition, many patients suffer from complications related to available therapies that are highly detrimental to their quality of life. New treatment modalities are, thus, urgently needed to further improve the efficacy and reduce the toxicity of existing therapies. Since antibodies specific for O-acetyl GD2 ganglioside display pro-apoptotic activity against neuroblastoma cells, we hy- pothesized that combination of immunotherapy could enhance tumor efficacy of neuroblastoma chemotherapy. MATERIAL AND METHODS Studies were done using Anti-OAcGD2 mAb 8B6 (IgG2a, kappa) previously obtained in our labo- ratory. An isotype-control mAb (DOTA-IgG2a, kappa) was used as a negative control. Evaluated chemotherapy was Topotecan. Human cell lines (LAN1, LAN5 and IMR5) were used for in vitro studies and mouse cell line NXS2 for in vitro and in vivo evaluation. Topotecan and mAb 8B6 interactions were analyzed for synergistic, additive, or antagonistic effect using the combination index (CI) method developed by Chou and Talalay. RESULTS We demonstrate here that combination of anti-O-acetyl GD2 monoclonal antibody 8B6 with topotecan synergistically inhibited neuroblastoma cell proliferation, as shown by the combination index values. Mechanistically, we evidence that mAb 8B6 induced plasma cell membrane lesions, consistent with oncosis. Neuroblastoma tumour cells treated with mAb 8B6 indeed showed an in- creased uptake of topotecan by the tumor cells and a more profound tumor cell death evidenced by increased caspase-3 activation. We also found that the combination with topotecan plus monoclonal antibody 8B6 showed a more potent anti-tumor efficacyin vivothan either agent alone. Importantly, we used low-doses of topotecan with no noticeable side effect. CONCLUSIONS Our data suggest that chemo-immunotherapy combinations may improve the clinical efficacy and safety profile of current chemotherapeutic modalities of neuroblastoma. 16:38–17:05 Discussion