Patient-specific clonal neoantigen peptide–HLA complex (Neoantigen-HLA complex)

Patient-specific clonal neoantigen peptide–HLA complexes are unique molecular targets formed when mutated proteins, resulting from somatic DNA alterations in tumor cells, are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules. Unlike shared tumor antigens, these neoantigens are entirely absent from normal tissues, making them highly specific targets for the immune system and reducing the risk of central thymic tolerance. Clonal neoantigens are particularly valuable as they are derived from early 'trunk' mutations present in all or most cells of a tumor, minimizing the impact of intratumoral heterogeneity. These complexes serve as the primary recognition site for T-cell receptors (TCRs), which can be leveraged through personalized cancer vaccines, TCR-engineered T-cell (TCR-T) therapies, and neoantigen-specific antibodies. By targeting these complexes, therapies aim to induce a robust and specific cytotoxic T-cell response that selectively eliminates malignant cells while sparing healthy ones. The clinical success of targeting these complexes depends heavily on accurate neoantigen prediction algorithms and the patient's specific HLA haplotype.

Other names

Tumor-specific neoantigen-MHC complexNeoepitope-HLA complexPersonalized neoantigen-HLA complexClonal neoantigen-HLA complexpHLA complex

Binding of therapeutic T-cell receptors (TCRs) or vaccine-induced endogenous TCRs to the specific peptide-HLA complex to trigger cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells.