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

Manuri PV, Wilson MH, Maiti SN, Mi T, Singh H, Olivares S, Dawson MJ, Huls H, Lee DA, Rao PH, Kaminski JM, Nakazawa Y, Gottschalk S, Kebriaei P, Shpall EJ, Champlin RE, Cooper LJ
Hum Gene Ther. 2010 21 (4): 427-37

PMID: 19905893 · PMCID: PMC2938363 · DOI:10.1089/hum.2009.114

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.

MeSH Terms (18)

Antigen-Presenting Cells Antigens, CD19 Cell Line, Tumor Cells, Cultured Coculture Techniques DNA Transposable Elements Electroporation Genetic Therapy Genetic Vectors Glioblastoma Humans K562 Cells Lymphoma, B-Cell Plasmids Receptors, Antigen T-Lymphocytes Transgenes Transposases

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