Efficient nonviral Sleeping Beauty transposon-based TCR gene transfer to peripheral blood lymphocytes confers antigen-specific antitumor reactivity

P. D. Peng, C. J. Cohen, S. Yang, C. Hsu, S. Jones, Y. Zhao, Z. Zheng, S. A. Rosenberg, R. A. Morgan

Research output: Contribution to journalArticle

Abstract

Genetically engineered lymphocytes hold promise for the treatment of genetic disease, viral infections and cancer. However, current methods for genetic transduction of peripheral blood lymphocytes rely on viral vectors, which are hindered by production and safety-related problems. In this study, we demonstrated an efficient novel nonviral platform for gene transfer to lymphocytes. The Sleeping Beauty transposon-mediated approach allowed for long-term stable expression of transgenes at ∼50% efficiency. Utilizing transposon constructs expressing tumor antigen-specific T-cell receptor genes targeting p53 and MART-1, we demonstrated sustained expression and functional reactivity of transposon-engineered lymphocytes on encountering target antigen presented on tumor cells. We found that transposon- and retroviral-modified lymphocytes had comparable transgene expression and phenotypic function. These results demonstrate the promise of nonviral ex vivo genetic modification of autologous lymphocytes for the treatment of cancer and immunologic disease.

Original languageEnglish (US)
Pages (from-to)1042-1049
Number of pages8
JournalGene Therapy
Volume16
Issue number8
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Peng, P. D., Cohen, C. J., Yang, S., Hsu, C., Jones, S., Zhao, Y., Zheng, Z., Rosenberg, S. A., & Morgan, R. A. (2009). Efficient nonviral Sleeping Beauty transposon-based TCR gene transfer to peripheral blood lymphocytes confers antigen-specific antitumor reactivity. Gene Therapy, 16(8), 1042-1049. https://doi.org/10.1038/gt.2009.54