DNAJB1-PRKACA fusion neoepitope–HLA complex (DNAJB1-PRKACA neoantigen-HLA)

The DNAJB1-PRKACA fusion neoepitope–HLA complex is a tumor-specific molecular target primarily associated with fibrolamellar carcinoma (FLC), a rare liver malignancy [1]. This complex is formed when a unique junctional peptide, resulting from the fusion of the DNAJB1 and PRKACA genes, is processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules [2]. The DNAJB1-PRKACA fusion is considered pathognomonic for FLC, occurring in nearly 100% of cases, which makes the resulting neoepitope an ideal candidate for targeted immunotherapy [1][4]. Because the fusion sequence is absent in healthy tissues, therapies targeting this complex are expected to have high specificity and minimal off-target effects. Current clinical strategies include the development of peptide vaccines and T-cell receptor (TCR) engineered T-cell therapies that specifically recognize the neoepitope in the context of certain HLA alleles, such as HLA-A*02:01 [2][3]. These immunotherapies aim to stimulate a robust cytotoxic T-lymphocyte response to selectively eliminate cancer cells expressing the chimeric protein. Research continues to explore the diversity of HLA alleles capable of presenting this neoantigen to broaden the patient population eligible for such treatments [2].

Other names

DNAJB1-PRKACA fusion peptide-MHC complexFibrolamellar carcinoma fusion neoantigenDNAJB1-PRKACA chimeric protein epitopeFLC fusion neoepitope-HLA complex

Induction of a targeted cytotoxic T-lymphocyte (CTL) response through the recognition of the tumor-specific fusion neoepitope presented by HLA molecules, leading to the selective lysis of malignant cells expressing the DNAJB1-PRKACA fusion protein [2][3].