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

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 M Kaminski, Yozo Nakazawa, Stephen Gottschalk, Partow Kebriaei, Elizabeth J Shpall, Richard E Champlin, Laurence J N Cooper
Human Gene Therapy 2010, 21 (4): 427-37
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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