BioCentury
ARTICLE | Translation in Brief

Two ways to reverse CAR T cell exhaustion; plus a ligand and its receptor in a single vector, Cleave, Amazentis and Cello

BioCentury’s roundup of translational news

April 9, 2021 5:37 PM UTC

A Stanford University team led by Crystal Mackall, co-founder of Lyell Immunopharma Inc. and Obsidian Therapeutics Inc., described in Science two ways to prevent or reverse CAR T cell exhaustion. The first is based on a CAR modified with a C-terminal destabilizing domain (DD) to enable drug-dependent control of CAR protein levels. The second is dependent on transient exposure to kinase inhibitor Sprycel dasatinib from Bristol Myers Squibb Co. (NYSE:BMY), which reversibly inhibits T cell receptor and CAR signaling. Both methods induced epigenetic reprogramming and restored functionality of exhausted CAR T cells. The authors hold patents covering both methods. Lyell is developing CAR-based therapies for solid tumors and Obsidian is developing regulatable CAR T cell therapies based on the DD technology.

Receptor and ligand expression in a single gene therapy vector increases therapeutic effect
An article in Science Advances suggests that simultaneous administration of a ligand and its receptor by a single gene therapy vector improves therapeutic efficacy compared to either receptor administration or ligand administration alone. The University of Melbourne and University of Cambridge scientists demonstrated enhanced axonal transport and therapeutic effect in glaucoma and tauopathy mouse models using a combination of BDNF and its receptor NTRK2 in a single vector. Both companies affiliated with the publication, Quethera Ltd., acquired by Astellas Pharma Inc. (Tokyo:4503) in 2018, and Ikarovec Ltd., are developing ophthalmic gene therapies...