Matthew Wilson
Last active: 3/28/2019

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

O'Neil RT, Saha S, Veach RA, Welch RC, Woodard LE, Rooney CM, Wilson MH
Nat Commun. 2018 9 (1): 1325

PMID: 29636469 · PMCID: PMC5893599 · DOI:10.1038/s41467-018-03787-8

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.

MeSH Terms (17)

Adoptive Transfer Animals Cell- and Tissue-Based Therapy Cell Engineering DNA Transposable Elements Erythropoietin Gene Expression Genetic Vectors Hematopoiesis Herpesvirus 4, Human Humans Mice Ovalbumin Receptors, Antigen, T-Cell T-Lymphocytes Transgenes Vaccination

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