ARTICLE | Translation in Brief

Reversible control of CAR expression; plus an inflammation-reducing mAb, two intranasal COVID-19 treatments and more

BioCentury’s roundup of translational news

December 21, 2020 10:42 PM UTC

Reversible regulation of chimeric antigen receptor expression
An article in Cell Chemical Biology takes advantage of a therapeutic strategy growing in popularity, targeted protein degradation, to reversibly control expression of type I membrane proteins, including CARs. The Novartis Institutes for BioMedical Research scientists genetically fused an AIOLOS-based sequence that triggers protein degradation in the presence of an IMiD to a CD19-targeted CAR and injected the “CAR19-degron” into mice with acute lymphoblastic leukemia. The CAR19-degron was able to kill CD19-positive cells to clear the tumor, and was then degraded upon treatment with Revlimid lenalidomide from Bristol Myers Squibb Co. (NYSE:BMY). 

Blocking an another interleukin pathway reduces inflammation
In Science ImmunologyRegeneron Pharmaceuticals Inc. (NASDAQ:REGN) researchers created a mouse model of a rare inflammatory disease dubbed deficiency of IL-36 receptor antagonist (DITRA) and used it to show that dysregulated IL–36R signaling leads to proinflammatory responses in the skin that are relevant to psoariasis and in the intestinal epithelium that could contribute to inflammatory bowel disease. An anti-IL36R mAb ameliorated the phenotypes...