Autolus Therapeutics announces publication in Nature Communications

Autolus Therapeutics announces a publication in Nature Communications entitled: ‘Structure-Guided Engineering of Immunotherapies Targeting TRBC1 and TRBC2 in T Cell Malignancies.’ The targetable difference between TRBC1 and TRBC2 is very small – merely a 2 amino acid inversion. In this publication, the research team at Autolus first describe the structural basis for selective AUTO4 CAR recognition of TRBC1. This structure shows that some amino acid residues stabilize the interaction with the TCR generally, while others result in selectivity. By exploiting this structure, the research team used in silico design and phage display to flip selectivity of the AUTO4 binder from TRBC1 to TRBC2 to generate AUTO5, a TRBC2-specific CAR T cell therapeutic. “The development of a TRBC2-specific therapeutic by in silico design is a tour-de-force of structural biology and protein engineering from the research team at Autolus,” said Dr Martin Pule Chief Scientific Officer and founder of Autolus. “T cell malignancies are a neglected clinical area and the development of AUTO5 along with AUTO4 could allow us to develop a broad therapeutic approach that exploits TRBC1/2 TCR biology.”