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PRAME mTCR CAR T is an experimental chimeric antigen receptor (CAR) T-cell therapy designed to target the intracellular antigen PRAME (Preferentially Expressed Antigen in Melanoma). Developed through a collaboration involving the Fred Hutchinson Cancer Research Center and Memorial Sloan Kettering Cancer Center, this therapy utilizes a TCR-mimic (mTCR) antibody fragment (clone Pr20) to recognize the PRAME-derived ALY peptide presented by HLA-A*02 on the cell surface. This approach overcomes the limitation of conventional CAR T cells, which are typically restricted to cell-surface proteins, by enabling the targeting of intracellular tumor-associated antigens. The CAR construct includes 4-1BB and CD3ζ signaling domains to drive T-cell activation and persistence. Preclinical data presented at ASH 2021 demonstrated that these CAR T cells exhibit potent, target-specific cytolytic activity against PRAME-positive acute myeloid leukemia (AML) cell lines and primary patient samples, with efficacy further enhanced by interferon-gamma (IFN-γ) treatment.
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