Development and characterization of naive single-type tumor antigen-specific CD8+ T lymphocytes from murine pluripotent stem cells

Fengyang Lei, Mohammad Haque, Praneet Sandhu, Swetha Ravi, Jianyong Song, Bing Ni, Songguo Zheng, Deyu Fang, Hongyan Jia, Jin Ming Yang, Jianxun Song

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4 Scopus citations

Abstract

Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination of in vitro priming through Notch ligands and in vivo development facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice. Three weeks later, B16 melanoma cells were inoculated subcutaneously, and the antitumor activity of the iPSC-derived T cells was assessed. We observed the development of the TRP2-specific iPSC-CD8+ T cells that responded to Ag stimulation and infiltrated into melanoma tissues, significantly inhibited the tumor growth, and improved the survival of the tumor-bearing mice. Thus, this approach may provide a novel effective strategy to treatment of malignant tumors.

Original languageEnglish (US)
Article numbere1334027
JournalOncoImmunology
Volume6
Issue number7
DOIs
StatePublished - Jul 3 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology

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    Lei, F., Haque, M., Sandhu, P., Ravi, S., Song, J., Ni, B., Zheng, S., Fang, D., Jia, H., Yang, J. M., & Song, J. (2017). Development and characterization of naive single-type tumor antigen-specific CD8+ T lymphocytes from murine pluripotent stem cells. OncoImmunology, 6(7), [e1334027]. https://doi.org/10.1080/2162402X.2017.1334027