title: T cells targeting NY-ESO-1 demonstrate efficacy against disseminated neuroblastoma.
abstract: The cancer-testis antigen NY-ESO-1 is expressed by many solid tumors and has limited expression by mature somatic tissues, making it a highly attractive target for tumor immunotherapy. Targeting NY-ESO-1 using engineered T cells has demonstrated clinical efficacy in the treatment of some adult tumors. Neuroblastoma is a significant cause of cancer mortality in children, and is a tumor type shown to be responsive to immunotherapies. We evaluated a large panel of primarily resected neuroblastoma samples and demonstrated that 23% express NY-ESO-1. After confirming antigen-specific activity of T cells genetically engineered to express an NY-ESO-1 directed high-affinity transgenic T cell receptorin vitro, we performed xenograft mouse studies assessing the efficacy of NY-ESO-1-targeted T cells in both localized and disseminated models of neuroblastoma. Disease responses were monitored by tumor volume measurement andin vivobioluminescence. After delivery of NY-ESO-1 transgenic TCR T cells, we observed significant delay of tumor progression in mice bearing localized and disseminated neuroblastoma, as well as enhanced animal survival. These data demonstrate that NY-ESO-1 is an antigen target in neuroblastoma and that targeted T cells represent a potential therapeutic option for patients with neuroblastoma.
authors.affiliation: Department of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Singh
authors.affiliation: Abramson Cancer Center and Department of Pathology, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Kulikovskaya
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia , Philadelphia, PA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Barrett
authors.affiliation: Adaptimmune , Abingdon, UK.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Binder-Scholl
authors.affiliation: Adaptimmune , Abingdon, UK.
authors.forename: Bent
authors.initials: B
authors.lastname: Jakobsen
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia , Philadelphia, PA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia , Philadelphia, PA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Pawel
authors.affiliation: Abramson Cancer Center and Department of Pathology, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , New York, NY, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kalos
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
keywords: Cell therapy; NY-ESO-1; immunotherapy; neuroblastoma; transgenic TCR