title: Chimeric antibody c.8B6 to O-acetyl-GD2 mediates the same efficient anti-neuroblastoma effects as therapeutic ch14.18 antibody to GD2 without antibody induced allodynia.
abstract: BACKGROUND
  Anti-GD2 antibody is a proven therapy for GD2-positive 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: ATLAB Pharma, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; INSERM U.892, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; CNRS 6299, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France.
authors: Mickaël
authors: M
authors: Terme
authors: ATLAB Pharma, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France.
authors: Mylène
authors: M
authors: Dorvillius
authors: INSERM U.892, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; CNRS 6299, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France.
authors: Denis
authors: D
authors: Cochonneau
authors: INSERM U.892, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; CNRS 6299, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; Université de Nantes, UFR des Sciences Pharmaceutiques et Biologiques, Nantes, France.
authors: Tanguy
authors: T
authors: Chaumette
authors: Department of Anesthesia, Mc Gill University, Montreal, Quebec, Canada.
authors: Wenhua
authors: W
authors: Xiao
authors: Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors: Mitchell B
authors: MB
authors: Diccianni
authors: INSERM U.892, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; CNRS 6299, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France.
authors: Jacques
authors: J
authors: Barbet
authors: Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America ; Center of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Alice L
authors: AL
authors: Yu
authors: INSERM U.892, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; CNRS 6299, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France.
authors: François
authors: F
authors: Paris
authors: Department of Anesthesiology, University of California San Diego School of Medicine, La Jolla, California, United States of America.
authors: Linda S
authors: LS
authors: Sorkin
authors: INSERM U.892, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; CNRS 6299, Centre de Recherche en Cancérologie de Nantes-Angers, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France ; Université de Nantes, UFR des Sciences Pharmaceutiques et Biologiques, Nantes, France.
authors: Stéphane
authors: S
authors: Birklé
mesh_terms: D000107:Acetylation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D005434:Flow Cytometry; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000473:pathology; D007275:Injections, Intravenous; D051379:Mice; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D005732:Gangliosides; C019403:ganglioside, GD2; C112746:dinutuximab