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 Kaminski,Yozo Nakazawa,Stephen Gottschalk,Partow Kebriaei,Elizabeth J. Shpall,Richard E. Champlin,Laurence J.N. Cooper
出处
期刊:Human Gene Therapy [Mary Ann Liebert] 日期:2009-11-11卷期号:21 (4): 427-437被引量:134
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.