HLA-presented DNAJB1-PRKACA fusion peptide

The HLA-presented DNAJB1-PRKACA fusion peptide is an immunogenic peptide epitope derived from the tumor-specific DNAJB1-PRKACA fusion protein, which is generated by a ~400 kb deletion on chromosome 19 that fuses the first exon of the DNAJB1 gene (a heat-shock protein family member) to exons 2–10 of the PRKACA gene (encoding the catalytic subunit of protein kinase A)[2][3]. This fusion is the pathognomonic driver of fibrolamellar hepatocellular carcinoma (FLC)[1][2][3]. The fusion protein is processed and presented on the surface of tumor cells by human leukocyte antigen (HLA) molecules as neoantigenic peptides. These HLA-restricted fusion peptides can be recognized by cytotoxic T cells, making them highly attractive for neoantigen-targeted immunotherapies, such as peptide-based vaccines and adoptive T-cell therapies[3][4][5]. Peptide vaccination targeting these neoepitopes in FLC patients has induced robust, polyfunctional, and durable T-cell responses, in some cases correlating with prolonged relapse-free survival[3][4][5]. Clinical trials are evaluating the safety and efficacy of DNAJB1-PRKACA fusion peptide vaccines, including FusionVAC-22, as well as their combination with immune checkpoint inhibitors[5]. Detection of these HLA-presented peptides and corresponding T cell responses may also serve as biomarkers for patient selection and monitoring treatment efficacy[3][4][5]. The main therapeutic challenge is the risk of off-tumor immune toxicity, but specificity for the fusion makes this risk lower than for non-tumor-restricted antigens[5].

Other names

DNAJB1-PRKACA fusion neoantigenDNAJB1-PRKACA fusion peptideDNAJB1-PRKACA fusion

Induction of T-cell–mediated immune response by vaccination with HLA-presented fusion-derived peptides triggers cytotoxic CD8+ and helper CD4+ T-cell responses against fusion-expressing tumor cells[3][4][5]. Immune checkpoint inhibitor (e.g. atezolizumab) potentiates anti-tumor activity by blocking PD-L1–mediated immune evasion, combined with peptide vaccine-induced T-cell priming[5].