48 / 238
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