Transposon-modified Antigen-specific T Lymphocytes for Sustained Therapeutic Protein Delivery in Vivo

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Apr 12

PMID 29636469

Citations 13

Authors

Richard T ONeil

Sunandan Saha

Ruth Ann Veach

Richard C Welch

Lauren E Woodard

Cliona M Rooney

Matthew H Wilson

Affiliations

Soon will be listed here.

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.

Citing Articles

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