Mutant RAS neoantigen-MHC complex (mRAS-MHC)

Mutant RAS neoantigen-MHC complexes are cell-surface targets formed when intracellular mutant RAS proteins (such as KRAS, NRAS, or HRAS) are processed by the proteasome into short peptides and presented by Major Histocompatibility Complex (MHC) molecules (1.1.1, 1.2.1). These complexes serve as highly specific neoantigens because the mutant peptide sequence is absent in healthy tissues, allowing the immune system to distinguish malignant cells from normal ones (1.1.5, 1.5.1). In many high-prevalence cancers, including pancreatic, colorectal, and lung adenocarcinomas, hotspot mutations at codons 12, 13, or 61 create these unique epitopes (1.3.1, 1.4.3). Therapeutic strategies targeting these complexes include T-cell receptor-engineered T-cell (TCR-T) therapies, cancer vaccines, and TCR-mimetic bispecific antibodies (1.3.4, 1.4.1). These treatments aim to bypass the historically undruggable nature of the intracellular RAS protein by leveraging the adaptive immune system to recognize and eliminate cells displaying the mutant epitope (1.4.3, 1.4.5). However, challenges such as low antigen density and the requirement for specific HLA allele matching, known as HLA restriction, remain significant hurdles in clinical development (1.1.4, 1.4.2).

Other names

RAS neoepitopesMutant RAS-HLA complexp-HLA complexRAS mutant peptide-MHCMutant RAS epitopes

T-cell receptor (TCR) binding and T-cell mediated cytotoxicity