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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

BioCentury’s roundup of translational news.

Dec 21, 2020 | 10:42 PM GMT

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.

NeuBase compound rescues mis-splicing in myotonic dystrophy models
NeuBase Therapeutics Inc. (NASDAQ:NBSE) said its preclinical peptide nucleic acid antisense oligo (ASO) rescued mis-splicing of RNA transcripts in a mouse model of myotonic dystrophy type 1 and in patient-derived fibroblasts. The company, which went public in 2019 via a reverse merger 11 months after launching, thinks its platform can access a broader range of targets than traditional ASOs, and overcome the modality’s delivery issues.

Eureka’s intranasal mAb prevents SARS-COV-2 infection
Eureka Therapeutics Inc. scientists reported in a bioRxiv preprint that administration of its intranasal anti-SARS-CoV-2 S mAb protected mice from SARS-CoV-2 infection for up to 10 hours. The mAb, dubbed EU126-M2, was modified to increase retention in respiratory mucosa. Eureka plans to submit an IND to FDA for a clinical trial of the mAb in a nasal spray formulation named InvisiMask.

Intranasal lentiviral vaccine protects against SARS-CoV-2 infection
Also in a bioRxiv preprint, researchers from the Institut Pasteur and Theravectys S.A. joint lab showed that intraperitoneal injection of a lentiviral vector COVID-19 vaccine, followed by an intranasal boost, decreased SARS-CoV-2 infection and lung inflammation in mice and hamsters.

TARGETS
AIOLOS (IKZF3) – IKAROS family zinc finger 3 
IL-36R (ILRL2) – Interleukin-1 (IL-1) receptor-like 2 
SARS-CoV-2 S – SARS-CoV-2 spike protein 

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