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

Nat Commun. 2018 Apr 10;9(1):1325. doi: 10.1038/s41467-018-03787-8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Engineering / methods
  • Cell- and Tissue-Based Therapy / methods*
  • DNA Transposable Elements / immunology*
  • Erythropoietin / genetics*
  • Erythropoietin / immunology
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Hematopoiesis / drug effects
  • Hematopoiesis / immunology
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Mice
  • Ovalbumin / administration & dosage
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation
  • Transgenes
  • Vaccination

Substances

  • DNA Transposable Elements
  • EPO protein, human
  • Receptors, Antigen, T-Cell
  • Erythropoietin
  • Ovalbumin