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Transposon-modified antigen-specific T lymphocytes for sustained therapeutic protein delivery in vivo

Author

Listed:
  • Richard T. O’Neil

    (Vanderbilt University School of Medicine
    Vanderbilt University School of Medicine)

  • Sunandan Saha

    (Baylor College of Medicine)

  • Ruth Ann Veach

    (Vanderbilt University School of Medicine
    Vanderbilt University School of Medicine)

  • Richard C. Welch

    (Vanderbilt University School of Medicine
    Vanderbilt University School of Medicine)

  • Lauren E. Woodard

    (Vanderbilt University School of Medicine
    Vanderbilt University School of Medicine
    Department of Veterans Affairs)

  • Cliona M. Rooney

    (Center for Cell and Gene Therapy, Baylor College of Medicine
    Department of Pediatrics, Baylor College of Medicine
    Department of Immunology, Baylor College of Medicine
    Department of Molecular Virology and Microbiology, Baylor College of Medicine)

  • Matthew H. Wilson

    (Vanderbilt University School of Medicine
    Vanderbilt University School of Medicine
    Department of Veterans Affairs)

Abstract

A cell therapy platform permitting long-term delivery of peptide hormones in vivo would be a significant advance for patients with hormonal deficiencies. Here we report the utility of antigen-specific T lymphocytes as a regulatable peptide delivery platform for in vivo therapy. piggyBac transposon modification of murine cells with luciferase allows us to visualize T cells after adoptive transfer. Vaccination stimulates long-term T-cell engraftment, persistence, and transgene expression enabling detection of modified cells up to 300 days after adoptive transfer. We demonstrate adoptive transfer of antigen-specific T cells expressing erythropoietin (EPO) elevating the hematocrit in mice for more than 20 weeks. We extend our observations to human T cells demonstrating inducible EPO production from Epstein–Barr virus (EBV) antigen-specific T lymphocytes. Our results reveal antigen-specific T lymphocytes to be an effective delivery platform for therapeutic molecules such as EPO in vivo, with important implications for other diseases that require peptide therapy.

Suggested Citation

  • Richard T. O’Neil & Sunandan Saha & Ruth Ann Veach & Richard C. Welch & Lauren E. Woodard & Cliona M. Rooney & Matthew H. Wilson, 2018. "Transposon-modified antigen-specific T lymphocytes for sustained therapeutic protein delivery in vivo," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03787-8
    DOI: 10.1038/s41467-018-03787-8
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