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

Richard T. O’Neil, Sunandan Saha, Ruth Ann Veach, Richard C. Welch, Lauren E. Woodard, Cliona M. Rooney and Matthew H. Wilson ()
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Richard T. O’Neil: Vanderbilt University School of Medicine
Sunandan Saha: Baylor College of Medicine
Ruth Ann Veach: Vanderbilt University School of Medicine
Richard C. Welch: Vanderbilt University School of Medicine
Lauren E. Woodard: Vanderbilt University School of Medicine
Cliona M. Rooney: Center for Cell and Gene Therapy, Baylor College of Medicine
Matthew H. Wilson: Vanderbilt University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03787-8

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DOI: 10.1038/s41467-018-03787-8

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