PiggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies

Pallavi V.Raja Manuri, Matthew H. Wilson, Sourindra N. Maiti, Tiejuan Mi, Harjeet Singh, Simon Olivares, Margaret J. Dawson, Helen Huls, Dean A. Lee, Pulivarthi H. Rao, Joseph M. Kaminski, Yozo Nakazawa, Stephen Gottschalk, Partow Kebriaei, Elizabeth J. Shpall, Richard E. Champlin, Laurence J.N. Cooper

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Nonviral integrating vectors can be used for expression of therapeutic genes. piggyBac (PB), a transposon/transposase system, has been used to efficiently generate induced pluripotent stems cells from somatic cells, without genetic alteration. In this paper, we apply PB transposition to express a chimeric antigen receptor (CAR) in primary human T cells. We demonstrate that T cells electroporated to introduce the PB transposon and transposase stably express CD19-specific CAR and when cultured on CD19+ artificial antigen-presenting cells, numerically expand in a CAR-dependent manner, display a phenotype associated with both memory and effector T cell populations, and exhibit CD19-dependent killing of tumor targets. Integration of the PB transposon expressing CAR was not associated with genotoxicity, based on chromosome analysis. PB transposition for generating human T cells with redirected specificity to a desired target such as CD19 is a new genetic approach with therapeutic implications.

Original languageEnglish (US)
Pages (from-to)427-437
Number of pages11
JournalHuman Gene Therapy
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Manuri, P. V. R., Wilson, M. H., Maiti, S. N., Mi, T., Singh, H., Olivares, S., Dawson, M. J., Huls, H., Lee, D. A., Rao, P. H., Kaminski, J. M., Nakazawa, Y., Gottschalk, S., Kebriaei, P., Shpall, E. J., Champlin, R. E., & Cooper, L. J. N. (2010). PiggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies. Human Gene Therapy, 21(4), 427-437. https://doi.org/10.1089/hum.2009.114