title: piggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies.
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.
authors.affiliation: Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Pallavi V Raja
authors.initials: PV
authors.lastname: Manuri
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Wilson
authors.forename: Sourindra N
authors.initials: SN
authors.lastname: Maiti
authors.forename: Tiejuan
authors.initials: T
authors.lastname: Mi
authors.forename: Harjeet
authors.initials: H
authors.lastname: Singh
authors.forename: Simon
authors.initials: S
authors.lastname: Olivares
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Dawson
authors.forename: Helen
authors.initials: H
authors.lastname: Huls
authors.forename: Dean A
authors.initials: DA
authors.lastname: Lee
authors.forename: Pulivarthi H
authors.initials: PH
authors.lastname: Rao
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Kaminski
authors.forename: Yozo
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D018941:Antigens, CD19 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D004251:DNA Transposable Elements / Q000235:genetics / Q000276:immunology; D018274:Electroporation; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D005909:Glioblastoma; D006801:Humans; D020014:K562 Cells; D016393:Lymphoma, B-Cell / Q000628:therapy*; D010957:Plasmids; D011946:Receptors, Antigen / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019076:Transgenes; D019895:Transposases / Q000235:genetics / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D004251:DNA Transposable Elements; D011946:Receptors, Antigen; D019895:Transposases