期刊
PLOS ONE
卷 9, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0087210
关键词
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资金
- Agence Nationale pour la Recherche [ANR 13 RPIB 0001 02 - GANGSTEMAB]
- Fondation de Projet de l'Universite de Nantes
- AAIR LICHENS
- Nantes Metropole
- Fondation de la Recherche Medicale
- Societe Francaise de lutte contre les Cancers et les leucemies de l'Enfant et de l'adolescent, l'Etoile de Martin, les Bagouz' a Manon, la Ligue contre le Cancer
- National Institutes of Health (NIH) [CA164132]
Background: Anti-GD2 antibody is a proven therapy for GD2-postive neuroblastoma. Monoclonal antibodies against GD2, such as chimeric mAb ch14.18, have become benchmarks for neuroblastoma therapies. Pain, however, can limit immunotherapy with anti-GD2 therapeutic antibodies like ch14.18. This adverse effect is attributed to acute inflammation via complement activation on GD2-expressing nerves. Thus, new strategies are needed for the development of treatment intensification strategies to improve the outcome of these patients. Methodology/ Principal Findings: We established the mouse-human chimeric antibody c.8B6 specific to OAcGD2 in order to reduce potential immunogenicity in patients and to fill the need for a selective agent that can kill neuroblastoma cells without inducing adverse neurological side effects caused by anti-GD2 antibody immunotherapy. We further analyzed some of its functional properties compared with anti-GD2 ch14.18 therapeutic antibody. With the exception of allodynic activity, we found that antibody c.8B6 shares the same anti-neuroblastoma attributes as therapeutic ch14.18 anti-GD2 mAb when tested in cell-based assay and in vivo in an animal model. Conclusion/Significance: The absence of OAcGD2 expression on nerve fibers and the lack of allodynic properties of c.8B6-which are believed to play a major role in mediating anti-GD2 mAb dose-limiting side effects-provide an important rationale for the clinical application of c.8B6 in patients with high-risk neuroblastoma.
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