Fms-like tyrosine kinase 3 D835H neoepitope presented by HLA-A*02:01 (FLT3-D835H/HLA-A*02:01)

The FLT3 D835H neoepitope presented by HLA-A*02:01 is a tumor-specific antigen resulting from a point mutation in the activation loop of the Fms-like tyrosine kinase 3 (FLT3) receptor. This mutation, which replaces aspartic acid with histidine at position 835, is a common driver in acute myeloid leukemia (AML) and contributes to constitutive kinase activity and resistance to certain tyrosine kinase inhibitors. When processed by the proteasome, the mutant protein yields a unique peptide sequence that is loaded onto HLA-A*02:01 molecules and displayed on the cell surface. This peptide-MHC complex serves as a highly specific target for immunotherapy, as it is absent from healthy tissues. Therapeutic strategies focusing on this target include the development of T-cell receptor-engineered T-cell (TCR-T) therapies and personalized neoantigen vaccines designed to elicit a robust cytotoxic T-cell response against the leukemic clones. By specifically targeting the D835H neoepitope, these treatments aim to achieve high precision while minimizing the systemic toxicities often associated with conventional chemotherapy or non-selective kinase inhibitors.

Other names

FLT3 D835H neoantigenHLA-A*02:01-restricted FLT3 D835H peptideFLT3 D835H pMHC complexFms-related receptor tyrosine kinase 3 D835H mutant epitope

Targeting of the specific peptide-MHC complex by engineered T-cell receptors (TCRs) or antibodies to induce selective cytotoxic T-lymphocyte mediated lysis of leukemia cells harboring the FLT3 D835H mutation.