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Hu8F4-CAR is a second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target the leukemia-associated antigen PR1 presented by HLA-A2. Developed by researchers at MD Anderson Cancer Center, this TCR-like CAR utilizes the Hu8F4 antibody fragment to recognize the PR1/HLA-A2 complex on the surface of malignant cells. PR1 is a 9-amino acid peptide derived from the myeloid azurophil granule proteins proteinase 3 (PR3) and neutrophil elastase (NE). Recent research has focused on optimizing the construct using a novel codon-based approach, replacing endogenous codons with rare synonymous isoforms in the non-antigen binding domains to modulate expression levels. This strategy aims to reduce on-target, off-tumor toxicity against healthy myeloid cells while preserving potent anti-tumor activity against acute myeloid leukemia (AML) cells.
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