allogeneic anti-CD83 CAR-T cells

Allogeneic anti-CD83 CAR-T cells are an investigational, CRISPR/Cas9 gene-edited cell therapy developed by CRISPR Therapeutics for the treatment of acute myeloid leukemia (AML) and graft-versus-host disease (GvHD). The therapy targets CD83, a protein expressed on AML blasts and allo-activated immune cells that mediate GvHD. The cells are engineered using CRISPR/Cas9 technology to include multiple genetic modifications: disruption of the T-cell receptor alpha constant (TRAC) gene to reduce the risk of GvHD, disruption of the Beta-2 microglobulin (B2M) gene to minimize allogeneic rejection by the host immune system, and knockout of the CD83 gene to prevent CAR-T cell fratricide. To further enhance potency and overcome T-cell exhaustion, the genes ZC3H12A (encoding Regnase-1) and TGFBR2 (encoding TGF-β receptor II) are also disrupted. The anti-CD83 CAR construct is site-specifically inserted into the TRAC locus. Preclinical data have demonstrated potent anti-tumor activity and effective prevention of GvHD in animal models.

Other names

CRISPR-edited anti-CD83 CAR-T cellsR/T/83 KO cells