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

Published

Journal Article

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 approximately 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.

Full Text

Cited Authors

  • Peng, PD; Cohen, CJ; Yang, S; Hsu, C; Jones, S; Zhao, Y; Zheng, Z; Rosenberg, SA; Morgan, RA

Published Date

  • August 2009

Published In

Volume / Issue

  • 16 / 8

Start / End Page

  • 1042 - 1049

PubMed ID

  • 19494842

Pubmed Central ID

  • 19494842

Electronic International Standard Serial Number (EISSN)

  • 1476-5462

International Standard Serial Number (ISSN)

  • 0969-7128

Digital Object Identifier (DOI)

  • 10.1038/gt.2009.54

Language

  • eng