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Oncoimmunology. 2017 Sep 21;7(1):e1373232. doi: 10.1080/2162402X.2017.1373232. eCollection 2017.

Neuroblastoma chemotherapy can be augmented by immunotargeting O-acetyl-GD2 tumor-associated ganglioside.

Author information

1
CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, Loire Atlantique, France.
2
Service de chirurgie pédiatrique, CHU de Nantes, 38 boulevard Jean Monnet, Nantes, Loire Atlantique, France.
3
Université de Nantes, UFR des Sciences Pharmaceutiques et Biologiques, 9 rue Bias, Nantes, Loire Atlantique, France.
4
INSERM, UMRS 1229, RMeS "Regenerative Medicine and Skeleton", CHU Nantes, PH4 OTONN, Université de Nantes, UFR Odontologie, SC3M Plateform, UMS INSERM 016 - CNRS 3556, SFR François Bonamy, 1 place Alexis Ricordeau, Nantes, Loire Atlantique, France.
5
Université de Nantes, UFR de Médecine, 1 rue Gaston Veil, Nantes, Loire Atlantique, France.
6
Service d'oncologie pédiatrique, CHU de Nantes, quai Moncousu, Nantes, Loire Atlantique, France.

Abstract

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 hypothesized that combination of immunotherapy could enhance tumor efficacy of neuroblastoma chemotherapy. 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 increased 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 efficacy in vivo than either agent alone. Importantly, we used low-doses of topotecan with no noticeable side effect. Our data suggest that chemo-immunotherapy combinations may improve the clinical efficacy and safety profile of current chemotherapeutic modalities of neuroblastoma.

KEYWORDS:

Chemoimmunotherapy; Neuroblastoma; O-Acetyl-GD2; Therapeutic Antibody; Topotecan

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