T cells targeting NY-ESO-1 demonstrate efficacy against disseminated neuroblastoma

Nathan Singh, Irina Kulikovskaya, David M. Barrett, Gwendolyn Binder-Scholl, Bent Jakobsen, Daniel Martinez, Bruce Pawel, Carl H. June, Michael D. Kalos, Stephan A. Grupp

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 receptor in 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 and in vivo bioluminescence. 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.

Original languageEnglish
JournalOncoImmunology
Volume5
Issue number1
DOIs
StatePublished - 2016

Keywords

  • Cell therapy
  • Immunotherapy
  • NY-ESO-1
  • Neuroblastoma
  • Transgenic TCR

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