TCR mimic CAR T cells targeting PRAME/HLA-A2 Chimeric antigen receptor (CAR) that bind Preferentially Expressed Antigen in Melanoma (PRAME) ALYVDSLFFL (ALY) / HLA-A*0201 (HLA-A2) to treat PRAME-expressing cancers. PRAME is aberrantly expressed in childhood and adult AML and is absent in normal hematopoietic cells, providing an ideal target for adoptive T cell therapy. Dr. Soheil Meshinchi at the Fred Hutch has developed CAR T cells targeting the PRAME antigen in AML (referred to as PRAME mTCR CAR T cells). This CAR includes a binding domain derived from the Pr20, and a TCR mimic antibody that recognize PRAME AYL epitope in complex with HLA-A2. These mTCR CAR T cells showed strong in vitro efficacy against HLA-A2 restricted AML cell lines expressing the PRAME antigen and primary AML patient samples. In vivo cell-derived xenograft models treated with PRAME mTCR CAR T cells demonstrated potent leukemia clearance and improved survival compared to unmodified T cell controls. Additionally, co-administering interferon gamma increased PRAME expression by cancer cells, which enhanced the cytolytic activity of PRAME mTCR CAR T cells. These results support the evaluation of PRAME mTCR CAR T cells in clinical trials for refractory/relapsed AML and in a variety of solid tumors <ul> <li>Adoptive CAR T cell therapy to treat t(8;21) AML, Inv(16) AML, or KMT2A-r AML</li> <li>Treatment for PRAME expressing-cancers, such as breast cancer, sarcoma, or neuroblastoma</li> </ul> <ul> <li>Novel CAR T cell therapy for pediatric and adult AML, which lack disease-specific surface protein target</li> <li>Targeting intracellular protein instead of lineage markers, such as CD33 and CD123, avoids the risk of long-lasting or even permanent myelosuppression</li> <li>PRAME is one of the highest expressing genes in AML, and overexpressed in a variety of cancers and hematologic malignancies</li> </ul> <ul> <li>Soheil Meshinchi, MD, PhD – Professor, Clinical Research Division</li> </ul> Preclinical in vivo Patent pending 23-023_PRAME_TCRm.pdf |cell therapy |TCR| CAR | t cell receptor| Soheil Meshinchi | TCR mimic | interferon gamma treatment | leukemia | Solid cancer | AML prame-tcrmimic-23-023