RAS neoantigen peptide–Major Histocompatibility Complex (MHC) (RAS-pMHC)

RAS neoantigen peptide–Major Histocompatibility Complex (MHC) complexes are specialized molecular targets formed when mutated RAS proteins, such as KRAS G12D or G12V, are intracellularly processed and presented on the cell surface by MHC class I molecules (Leidner et al., 2022, NEJM). These complexes are highly tumor-specific because the driver mutations are absent in healthy tissues, making them ideal candidates for TCR-based immunotherapies (Neogene Therapeutics, 2023). T-cell receptor (TCR) engineered T cells, such as NEO-STC-01, are designed to recognize these specific peptide-HLA combinations with high sensitivity and specificity (AstraZeneca/Neogene, 2023). Upon recognition, the TCR-T cell undergoes activation and expansion, leading to the targeted lysis of the cancer cell through the secretion of cytotoxic cytokines and pro-apoptotic factors (Sim et al., 2020, Cancer Immunology Research). This therapeutic approach is particularly relevant for solid tumors with high RAS mutation frequencies, such as pancreatic ductal adenocarcinoma and colorectal cancer (ClinicalTrials.gov, 2022). However, therapeutic success depends on the stable expression of MHC molecules and the presence of the specific HLA allele required for peptide presentation (PubMed, 2021).

Other names

KRAS neoantigen-HLA complexMutated RAS peptide-MHCRAS pMHCKRAS G12D-HLA-A*11:01 complexKRAS G12V-HLA-A*03:01 complexRAS neoantigen-MHC class I complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-cell activation and tumor cell lysis.