Transposon-modified antigen-specific T lymphocytes for sustained therapeutic protein delivery in vivo.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29636469.
- Also identified by DOI 10.1038/s41467-018-03787-8 and PMC identifier 5893599.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Cell- and Tissue-Based Therapy
- DNA Transposable Elements
- Erythropoietin
- Receptors, Antigen, T-Cell
- T-Lymphocytes