Kirkey DC, Loeb A, Castro S, et al. Therapeutic Targeting PRAME with mTCRCAR T Cells in Acute Myeloid Leukemia. Blood Advances. 2022; (doi: 10.1182/bloodadvances.2022008304).
Research suggests that immunotherapy directed at Preferentially Expressed Antigen in Melanoma (PRAME), a cancer testes antigen, is a promising intervention for acute myeloid leukemia (AML). PRAME is an ideal target because it is present in many pediatric and adult AML cases but is not expressed in healthy hematopoietic cells. Investigators mapped out a novel method of targeting the intracellular antigen with the help of a chimeric antigen receptor (CAR) construct. The construct encodes a targeting domain that is based on T cell receptor (TCR) mimic antibodies and that targets the peptide:HLA complex. The TCR mimic antibody Pr20 is known to recognize PRAME ALY peptide in complex with HLA-A*02. Researchers used this existing antibody to generate CAR T cells (PRAME mTCRCAR T) that exhibited robust anti-leukemia activity and improved survival compared with unmodified T-cells in xenograft models. PRAME mTCRCAR T also effectively targeted PRAME in vitro. Treating the target cells with interferon-gamma boosted PRAME antigen expression, thereby enhancing the cytolytic effect of mimic TCR CAR T cells.