RUNX1-RUNX1T1 fusion neoantigen peptide–major histocompatibility complex (AML1-ETO pMHC)

The RUNX1-RUNX1T1 (AML1-ETO) fusion neoantigen peptide–MHC complex is a highly specific therapeutic target found on the surface of acute myeloid leukemia (AML) cells harboring the t(8;21) translocation [PMID: 31110039]. This complex consists of a unique peptide sequence derived from the fusion junction of the RUNX1 and RUNX1T1 proteins, which is processed and presented by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 [PMID: 28814475]. Because the fusion sequence is entirely absent in healthy tissues, this pMHC complex serves as a public neoantigen, offering a narrow window for immunotherapy with minimal off-target effects [Nature Communications, 2019]. Therapeutic strategies targeting this complex include T-cell receptor (TCR)-engineered T cells and TCR-like antibodies or bispecific molecules [Blood, 2017]. These agents are designed to recognize the specific peptide-MHC configuration and trigger a potent cytotoxic immune response against the leukemic blasts. Despite its promise, challenges include the potential for immune escape through HLA loss and the requirement for specific HLA-matching in patients [Frontiers in Immunology, 2021]. The target is particularly valuable because the t(8;21) translocation is a primary driver of leukemogenesis, ensuring the antigen is present on the majority of malignant cells in affected patients. Clinical development focuses on patients who have relapsed or are refractory to standard chemotherapy, utilizing the immune system's specificity to eradicate residual disease.

Other names

AML1-ETO fusion neoantigent(8;21) fusion peptide-HLA complexRUNX1-RUNX1T1 neoepitope-MHCAML1-ETO pMHC complexRUNX1-RUNX1T1 fusion antigen

Targeted immune-mediated cytotoxicity via recognition of the fusion-derived neoepitope presented on MHC molecules by engineered T-cells or antibodies.