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CRISPR-CAR33-2 is an experimental allogeneic chimeric antigen receptor T-cell (CAR-T) therapy targeting the CD33 (Siglec-3) antigen, primarily developed for the treatment of acute myelogenous leukemia (AML). Developed by CRISPR Therapeutics, the therapy utilizes CRISPR/Cas9 gene editing to modify healthy donor-derived T cells. These modifications include the disruption of the T-cell receptor alpha constant (TRAC) locus to prevent graft-versus-host disease (GvHD) and the disruption of the beta-2-microglobulin (B2M) locus to eliminate MHC class I expression, thereby protecting the cells from host immune rejection. The anti-CD33 CAR construct is site-specifically inserted into the TRAC locus. Preclinical data distinguishes CRISPR-CAR33-2 from its sibling candidate, CRISPR-CAR33-1, by its specific cytokine profile, notably secreting lower levels of IL-2 while maintaining high IFN-gamma production upon engagement with AML cells.
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