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Universal, chimeric antigen receptor (CAR)-based T cell therapy using zinc finger nuclease (ZFN) T cell editing

T cells engineered to express a CD19-specific CAR and lack major histocompatibility complex class I A (HLA-A) could be used as a universal therapy to treat CD19+ cancers. Allogeneic, CAR-based T cell therapies are limited because of potential rejection of the engineered donor cells by the recipient. In human, CD19-specific CAR T cells, ZFN mRNAs were introduced by electrotransfer and shown to eliminate HLA-A expression during 50 days of coculture. The modified CD19-specific T cells evaded HLA-A-restricted cytotoxic T lymphocyte attack and maintained antitumor activity against patient-derived primary lymphoma cells. Next steps include clinical trials using CD19-specific T cells that lack T cell receptor (TCR) expression and CD19-specific T cells that lack TCR and HLA-A expression.

SciBX 6(27); doi:10.1038/scibx.2013.708
Published online July 18, 2013

Patent application filed; available for licensing from The University of Texas MD Anderson Cancer Center Office of Technology Commercialization
Contact: Emmanuelle Schuler, The University of Texas MD Anderson Cancer Center, Houston, Texas
e-mail:

eschuler@mdanderson.org

Torikai, H. et al. Blood; published online June 5, 2013;
doi:10.1182/blood-2013-03-478255
Contact: Laurence J.N. Cooper, The University of Texas MD Anderson Cancer Center, Houston, Texas
e-mail:

ljncooper@mdanderson.org