title: An Optimized GD2-Targeting Retroviral Cassette for More Potent and Safer Cellular Therapy of Neuroblastoma and Other Cancers.
abstract: Neuroblastoma is the commonest extra cranial solid cancer of childhood. Despite escalation of treatment regimens, a significant minority of patients die of their disease. Disialoganglioside (GD2) is consistently expressed at high-levels in neuroblastoma tumors, which have been targeted with some success using therapeutic monoclonal antibodies. GD2 is also expressed in a range of other cancer but with the exception of some peripheral nerves is largely absent from non-transformed tissues. Chimeric Antigen Receptors (CARs) are artificial type I proteins which graft the specificity of a monoclonal antibody onto a T-cell. Clinical data with early CAR designs directed against GD2 have shown some promise in Neuroblastoma. Here, we describe a GD2-targeting CAR retroviral cassette, which has been optimized for CAR T-cell persistence, efficacy and safety.
authors.affiliation: Cancer Institute, University College London, London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Karin
authors.initials: K
authors.lastname: Straathof
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Nourredine
authors.initials: N
authors.lastname: Himoudi
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Cancer Institute, University College London, London, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Pule
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005732:Gangliosides / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D016219:Immunotherapy, Adoptive; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D005732:Gangliosides; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C025447:sialogangliosides