PAX7-FOXO1 fusion protein-derived peptides presented on MHC (PAX7-FOXO1 neoantigen)

The PAX7-FOXO1 fusion protein-derived peptides presented on MHC are tumor-specific neoantigens resulting from the t(1;13)(p36;q14) chromosomal translocation characteristic of alveolar rhabdomyosarcoma (ARMS) (Shern et al., 2014, Cancer Discovery). This translocation fuses the DNA-binding domain of PAX7 with the transactivation domain of FOXO1, creating an oncogenic transcription factor that promotes cell proliferation and inhibits apoptosis (Gattenloehner et al., 2009, Journal of Pathology). While the fusion protein itself is an intracellular target, peptides derived from the unique breakpoint junction are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (Orentas et al., 2012, Frontiers in Oncology). These peptide-MHC complexes are ideal targets for immunotherapy because the breakpoint sequence is entirely absent in the normal human proteome, theoretically eliminating off-target toxicity. Therapeutic approaches currently under investigation include T-cell receptor (TCR) engineered T cells and neoantigen-based vaccines designed to prime the immune system against these specific epitopes (Lowery et al., 2017, Science). However, challenges such as HLA downregulation and the requirement for specific HLA alleles for peptide presentation remain significant hurdles in clinical application.

Other names

PAX7-FOXO1 neoepitopePAX7-FKHR fusion peptidePAX7-FOXO1 breakpoint peptidePAX7-FOXO1/HLA complex

T-cell receptor (TCR) mediated recognition of the specific fusion-derived peptide sequence presented by MHC molecules, leading to T-cell activation and targeted cytotoxic lysis of tumor cells.