Hu8F4-CAR(PQ)-T cells

Hu8F4-CAR(PQ)-T cells are an investigational second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target the leukemia-associated antigen PR1 presented by HLA-A2. The construct incorporates a humanized single-chain variable fragment (scFv) derived from the Hu8F4 antibody, a CD28 costimulatory domain, and a CD3ζ signaling domain. A defining feature of this specific version is the 'PQ' mutation in the human IgG1 CH2CH3 extracellular spacer domain, which involves replacing the ELLG (Glu-Leu-Leu-Gly) motif with PVA (Pro-Val-Ala) and an Asn-to-Gln (N to Q) substitution. These modifications are engineered to eliminate binding to Fc gamma receptors (FcgR) on innate immune cells, thereby preventing off-target activation and activation-induced cell death (AICD), which previously limited the in vivo persistence and anti-tumor activity of the parent Hu8F4-CAR construct. The therapy is being evaluated for the treatment of acute myeloid leukemia (AML) and other PR1-expressing hematologic malignancies.

Other names

Hu8F4-CAR(PQ) T cellsFc-mutated Hu8F4-CAR-T cells