AAV-ARCUS-CAR T cell vector

AAV-ARCUS-CAR T cell vector is an experimental in vivo gene therapy system designed to generate CAR T cells directly within the patient's body. Developed by researchers at Tel Aviv University and the Sourasky Medical Center, the system employs a single adeno-associated viral (AAV) vector that has been engineered with a CD8-specific designed ankyrin repeat protein (DARPin) to selectively target cytotoxic T cells. The vector co-encapsulates a chimeric antigen receptor (CAR) transgene and a cassette for the ARCUS nuclease, a proprietary genome-editing tool derived from the I-CreI homing endonuclease. ARCUS is designed to create a site-specific double-strand break at the T cell receptor alpha constant (TRAC) locus, allowing for the precise integration of the CAR transgene via homology-directed repair. This process simultaneously knocks out the endogenous T cell receptor (TCR) and places the CAR under the transcriptional control of the native TCR alpha promoter, potentially improving physiological regulation and reducing the risk of graft-versus-host disease (GVHD). This approach aims to bypass the complexities of ex vivo manufacturing and the need for lymphodepleting preconditioning in the treatment of hematological malignancies.

Other names

AAV-ARCUS-CAR TCD8-targeted AAV-ARCUS-CAR T vectorCD-8-targeted AAV-ARCUS-CAR T vectorCD 8-targeted AAV-ARCUS-CAR T vector