piggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies.
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.
Manuri
Pallavi V Raja
PV
Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wilson
Matthew H
MH
Maiti
Sourindra N
SN
Mi
Tiejuan
T
Singh
Harjeet
H
Olivares
Simon
S
Dawson
Margaret J
MJ
Huls
Helen
H
Lee
Dean A
DA
Rao
Pulivarthi H
PH
Kaminski
Joseph M
JM
Nakazawa
Yozo
Y
Gottschalk
Stephen
S
Kebriaei
Partow
P
Shpall
Elizabeth J
EJ
Champlin
Richard E
RE
Cooper
Laurence J N
LJ
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
D018941:Antigens, CD19; D004251:DNA Transposable Elements; D011946:Receptors, Antigen; D019895:Transposases