TY - JOUR
T1 - PiggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies
AU - Manuri, Pallavi V.Raja
AU - Wilson, Matthew H.
AU - Maiti, Sourindra N.
AU - Mi, Tiejuan
AU - Singh, Harjeet
AU - Olivares, Simon
AU - Dawson, Margaret J.
AU - Huls, Helen
AU - Lee, Dean A.
AU - Rao, Pulivarthi H.
AU - Kaminski, Joseph M.
AU - Nakazawa, Yozo
AU - Gottschalk, Stephen
AU - Kebriaei, Partow
AU - Shpall, Elizabeth J.
AU - Champlin, Richard E.
AU - Cooper, Laurence J.N.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
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U2 - 10.1089/hum.2009.114
DO - 10.1089/hum.2009.114
M3 - Article
C2 - 19905893
AN - SCOPUS:77950953208
SN - 1043-0342
VL - 21
SP - 427
EP - 437
JO - Human Gene Therapy
JF - Human Gene Therapy
IS - 4
ER -