T-cell receptor specific for Acute Myeloid Leukemia antigens (AML-specific TCR)

T-cell receptors (TCRs) specific for Acute Myeloid Leukemia (AML) antigens are engineered or naturally derived receptors designed to recognize specific peptide fragments of AML-associated proteins presented by Human Leukocyte Antigen (HLA) molecules (PubMed: 31515258). Unlike Chimeric Antigen Receptors (CARs) which recognize surface proteins, TCRs can target intracellular antigens, which constitute the majority of potential targets in AML, such as Wilms Tumor 1 (WT1), PRAME, and Proteinase 3 (PubMed: 30635445, PubMed: 28811303). Upon binding to the cognate antigen-HLA complex on the surface of leukemic blasts, the TCR initiates a signaling cascade involving the CD3 complex, leading to T-cell proliferation, cytokine release, and the direct killing of the cancer cells. This approach is particularly relevant for AML because many AML-specific markers are not expressed on the cell surface, making them inaccessible to traditional antibody-based or CAR-T therapies. Clinical development focuses on optimizing TCR affinity and ensuring safety by minimizing cross-reactivity with similar peptides in healthy tissues (PubMed: 29907163). These receptors are typically introduced into a patient's T cells via viral vectors or gene editing to create TCR-T cell therapies, which are currently being evaluated in various clinical trials for relapsed or refractory AML.

Other names

AML-specific T-cell receptorTCR-T for AMLWT1-specific TCRPRAME-specific TCRHA-1-specific TCR

Engineered T-cell receptors recognize specific AML-associated intracellular peptides presented by HLA molecules, triggering T-cell mediated cytotoxicity against leukemic blasts.