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Genetic Engineering Publications - GEG Tech top picks
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BigField GEG Tech's insight:
Present adoptive immunotherapy strategies to recognize tumor antigens are based on the genetic engineering of T-cells. In this study, the authors use megaTAL and CRISPR/Cas9 to disrupt T-cell receptor expression. They optimized the conditions for the delivery and assessed off target cleavage to give translatable manufacturing process to produce safe cellular substrates for next generation immunotherapies. 
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The researchers report a first-in-human phase I clinical trial to test the safety and feasibility of multiplex CRISPR-Cas9 editing to engineer T cells in three patients with refractory cancer. Two genes encoding the endogenous T cell receptor (TCR) chains, TCRα (TRAC) and TCRβ (TRBC) were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1). Removal of a third gene encoding PD-1 (PDCD1), was performed to improve anti-tumor immunity. Adoptive transfer of engineered T cells into patients resulted in durable engraftment with edits at all three genomic loci. Though chromosomal translocations were detected, the frequency decreased over time. Modified T cells persisted for up to 9 months suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of CRISPR gene-editing for cancer immunotherapy.