Precision BioSciences to Highlight Capabilities of ARCUS Gene Editing for Allogeneic CAR T Cell Immunotherapies at The Society for Immunotherapy of Cancer 36th Annual Meeting
Abstract Number & Title: Abstract #140. Allogeneic CAR T cells with Deoxycytidine Kinase Knockdown Demonstrate Resistance to Fludarabine
Category: Cellular Therapies
Abstracts for the SITC 36th Annual Meeting are now available on the SITC Annual Meeting website and in the
In this preclinical study, ARCUS gene editing was used to disrupt the endogenous T cell receptor by inserting a transgene carrying a CD19-specific CAR and an RNAi sequence designed to specifically knockdown deoxycytidine kinase (dCK), a protein that converts fludarabine from its prodrug form to an active compound. This single-step approach generated allogeneic, fludarabine-resistant (FluR) CAR T cells. In these cells, the dCK RNAi sequence produced a 70% reduction in dCK mRNA abundance, and resistance to fludarabine was confirmed in vitro. Additionally, treatment of tumor-bearing mice with fludarabine and FluR CAR T cells resulted in enhanced tumor clearance and survival compared to mice receiving control CAR T cells alone or control CAR T cells and fludarabine.
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