DNA4 Chimeric Autoantibody Receptor T cell (DNA4-CAART)

DNA4-CAART is a novel precision cellular immunotherapy designed to treat systemic lupus erythematosus (SLE) and lupus nephritis by selectively targeting and eliminating B cells that produce anti-double-stranded DNA (anti-dsDNA) autoantibodies. The therapy utilizes T cells engineered to express a chimeric autoantibody receptor (CAAR) that incorporates heparan sulphate as the extracellular antigen-binding domain. Heparan sulphate is a glycosaminoglycan that cross-reacts with anti-dsDNA antibodies, allowing the CAAR T cells to act as 'bait' to specifically recognize and kill autoreactive B cells via their B-cell receptors (BCRs). This approach aims to provide a causal treatment for SLE by depleting the pathogenic B-cell clones responsible for tissue damage while sparing healthy B cells necessary for protective immunity. Preclinical studies in immune-kidney organoid models have demonstrated that DNA4-CAART can reduce renal damage markers and improve organoid morphology by effectively clearing anti-dsDNA-positive B cells.

Other names

DNA4-CAARTDNA-CAARTDNA4 Chimeric Autoantibody ReceptorHeparan sulphate-based CAAR

Selective cytotoxicity against anti-dsDNA-producing B cells via CAAR-BCR interaction