12:16 PM
Feb 21, 2019
 |  BC Innovations  |  Emerging Company Profile

Refuge: Receptive CAR checkpoints

How Refuge is using CRISPR to suppress checkpoint genes in CAR T cells

Refuge Biotechnologies Inc. aims to make CAR T cells more potent by suppressing their checkpoint genes and is using a form of CRISPR that knocks the genes down instead of out to improve safety.

CEO Bing Wang told BioCentury that like endogenous T cells, CAR T cell therapies also express checkpoint proteins that can limit their anti-tumor activity.

Wang said Refuge designs its CARs to trigger checkpoint suppression by attaching a protease to the end of the intracellular domain. When the CAR is activated, the protease cleaves a linker joining a protein in its signaling pathway to catalytically dead Cas9 (dCas9). The freed dCas9, which can bind DNA and block its expression but cannot cleave it, then translocates to the nucleus where guide RNAs direct it to the target gene.

Refuge’s first two programs are preclinical autologous therapies in which CAR activation triggers suppression of PD-1...

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