An Optimized GD2-Targeting Retroviral Cassette for More Potent and Safer Cellular Therapy of Neuroblastoma and Other Cancers

PLoS One. 2016 Mar 31;11(3):e0152196. doi: 10.1371/journal.pone.0152196. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Gangliosides / immunology
  • Genetic Vectors
  • Humans
  • Immunoglobulin G / genetics
  • Immunotherapy, Adoptive*
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Neuroblastoma / immunology
  • Neuroblastoma / metabolism
  • Neuroblastoma / therapy*
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Retroviridae / genetics
  • Transduction, Genetic

Substances

  • Gangliosides
  • Immunoglobulin G
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • sialogangliosides