PAX3-FOXO1 fusion protein-derived peptide antigen (PAX3-FOXO1 peptide)

PAX3-FOXO1 fusion protein-derived peptide antigens are tumor-specific neoantigens arising from the chromosomal translocation t(2;13)(q35;q14), which is characteristic of alveolar rhabdomyosarcoma (ARMS) (Barr et al., 1993; NIH). This translocation results in a chimeric transcription factor that combines the DNA-binding domains of PAX3 with the transactivation domain of FOXO1, driving oncogenesis by dysregulating genes involved in growth and differentiation (Sorensen et al., 2002; PubMed). The unique amino acid sequence at the fusion breakpoint is not found in the normal human proteome, making it an ideal target for precision immunotherapy (Gier et al., 2023; Nature Communications). These peptides are processed intracellularly and presented on the cell surface by specific Human Leukocyte Antigen (HLA) molecules, such as HLA-A*02:01 (Dagher et al., 2002; PubMed). Current therapeutic strategies focus on utilizing these peptides in cancer vaccines or as targets for T-cell receptor (TCR) engineered T-cell therapies to induce a robust anti-tumor immune response (ClinicalTrials.gov). While highly specific, the efficacy of targeting these antigens can be limited by the tumor's ability to downregulate MHC expression or the inherently low density of the fusion peptide on the cell surface (Gier et al., 2023; Nature Communications).

Other names

PAX3-FKHR fusion protein-derived peptidePAX3-FOXO1 neoantigent(2;13) fusion peptideAlveolar rhabdomyosarcoma fusion peptide

Induction of a cytotoxic T lymphocyte (CTL) response against tumor cells by presenting unique fusion-junction peptides on Major Histocompatibility Complex (MHC) molecules (Dagher et al., 2002; PubMed).