Patient-specific clonal tumor neoantigen-Major Histocompatibility Complex (cNeT-MHC)

Patient-specific clonal tumor neoantigens are unique proteins arising from non-synonymous somatic mutations that occur early in tumorigenesis, ensuring their presence across all malignant cells within a patient's tumor (Achilles Therapeutics, 2024). These neoantigens are processed into peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, serving as the primary signal for T-cell recognition (McGranahan et al., Science, 2016). Because these antigens are absent from healthy tissues, they provide a highly specific therapeutic window, minimizing the risk of off-target autoimmune reactions (Schumacher & Schreiber, Science, 2015). TIDAL-02 is an autologous tumor-infiltrating lymphocyte (TIL) therapy that specifically targets these clonal neoantigens to overcome tumor heterogeneity (Achilles Therapeutics Pipeline, 2023). By focusing on these 'trunk' mutations, the therapy aims to eliminate the entire tumor mass and prevent immune escape mediated by subclonal loss (ClinicalTrials.gov, NCT05451849). This personalized approach utilizes advanced bioinformatics to identify and expand T-cells with the highest affinity for a patient's unique clonal neoantigen profile.

Other names

Clonal neoantigencNeTTumor-specific neoepitopePatient-specific neoantigenNeoantigen-HLA complex

Adoptive cell transfer of autologous tumor-infiltrating lymphocytes (TILs) specifically expanded to recognize and lyse tumor cells presenting clonal neoantigens on Major Histocompatibility Complex (MHC) molecules.