JAK2 V617F-derived neoantigen peptides presented on MHC (JAK2 V617F pMHC)

JAK2 V617F-derived neoantigen peptides presented on MHC represent a highly specific class of therapeutic targets for the treatment of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis (1.1.1, 1.4.1). The JAK2 V617F mutation is a somatic point mutation (valine to phenylalanine at codon 617) that leads to constitutive activation of the JAK-STAT signaling pathway and is present in the majority of MPN patients, including approximately 95% of those with polycythemia vera (1.3.4, 1.4.2). This mutation generates a unique amino acid sequence that can be processed into neoantigenic peptides, such as VLNYGVCFC and LVLNYGVCF, and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, primarily HLA-A*02:01 and HLA-B*35:01 (1.1.1, 1.1.5). Because these neoantigens are absent in healthy tissues, they provide an ideal target for precision immunotherapies such as peptide-based vaccines and T-cell receptor (TCR) engineered T-cell therapies (1.2.3, 2.3.4). Current research focuses on overcoming immune evasion mechanisms, such as the downregulation of MHC expression by malignant clones, and enhancing the infiltration of neoantigen-specific T cells into the bone marrow to achieve durable molecular remissions (1.1.1, 2.2.4). These therapies aim to selectively eradicate the malignant clone while sparing healthy hematopoietic cells, offering a potentially curative approach compared to standard symptom-modifying treatments (1.3.1, 1.3.2).

Other names

JAK2 V617F neoantigenJAK2 V617F neoepitopeJAK2 V617F mutant peptide-MHC complexJAK2 V617F pMHC

Therapeutic strategies targeting JAK2 V617F-derived neoantigen peptides presented on MHC aim to induce or enhance a cytotoxic T-lymphocyte (CTL) response against malignant cells. Peptide vaccines provide the specific mutant epitope to prime the immune system, while TCR-engineered T-cell therapies involve the adoptive transfer of T cells with receptors specifically designed to recognize the JAK2 V617F pMHC complex. These approaches lead to the selective lysis of cells harboring the driver mutation, potentially eradicating the malignant clone in myeloproliferative neoplasms.