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**TRAC-CD33-28z-CAR** is an experimental second-generation chimeric antigen receptor (CAR) T-cell therapy specifically designed for the treatment of acute myeloid leukemia (AML). The therapy targets **CD33** (Siglec-3), a transmembrane receptor highly expressed on AML blasts and leukemic stem cells (LSCs). This specific construct is engineered using homology-directed repair (HDR) to insert the CAR sequence into the **TRAC** (T-cell receptor alpha constant) locus, a strategy intended to promote stable expression and reduce T-cell exhaustion. The CAR signaling architecture includes a **CD28** costimulatory domain and a **CD3-zeta** activation domain. Preclinical data indicates that the CD28-containing construct (28z) exhibits high sensitivity, achieving significant cytolytic activity at lower antigen densities (approximately 741 antibodies bound per cell) compared to 4-1BB-based counterparts.
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