Glioblastoma cancer stem cell-specific peptide-Major Histocompatibility Complex (GCSC pMHC) (GCSC pMHC)

Glioblastoma cancer stem cell-specific antigens presented as peptide-MHC (pMHC) complexes are critical targets for advanced immunotherapy in glioblastoma multiforme (GBM). These complexes consist of intracellularly processed peptide fragments derived from proteins uniquely or over-expressed in glioblastoma cancer stem cells (GCSCs)—such as EGFRvIII, IL-13Rα2, or Survivin—bound to Major Histocompatibility Complex (MHC) molecules on the cell surface (Source: Brown et al., 2016, NEJM). Because GCSCs are primarily responsible for tumor initiation, therapeutic resistance, and post-treatment recurrence, targeting their specific pMHC signatures allows for the selective destruction of the tumor's regenerative core by T-cell receptors (TCRs) on cytotoxic T lymphocytes (Source: O'Rourke et al., 2017, Science Translational Medicine). Therapeutic strategies include peptide vaccines like ICT-107 and SurVaxM, as well as adoptive cell therapies using TCR-engineered T cells (Source: Ahluwalia et al., 2023, J Clin Oncol). Despite their potential, these targets face challenges such as the highly immunosuppressive glioblastoma microenvironment and antigen escape, where the tumor evolves to lose the target antigen under selective pressure (Source: Sampson et al., 2010, J Clin Oncol). Additionally, ensuring that these antigens are not expressed in healthy neural tissue is paramount to avoiding severe neurotoxicity.

Other names

GCSC-specific antigensGlioblastoma stem cell neoantigensGCSC pMHC complexesGlioblastoma cancer stem cell-specific antigens presented as peptide-MHC complexes to T cell receptors

T-cell mediated cytotoxicity via TCR recognition of peptide-MHC complexes