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Oncoimmunology. 2015 Aug 12;5(1):e1040216. eCollection 2016.

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

Author information

1
Department of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
2
Abramson Cancer Center and Department of Pathology, University of Pennsylvania , Philadelphia, PA, USA.
3
Division of Oncology, Children's Hospital of Philadelphia , Philadelphia, PA, USA.
4
Adaptimmune , Abingdon, UK.
5
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia , Philadelphia, PA, USA.
6
Lilly Research Laboratories, Eli Lilly and Company , New York, NY, USA.
7
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.

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.

KEYWORDS:

Cell therapy; NY-ESO-1; immunotherapy; neuroblastoma; transgenic TCR

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