Mutant RAS neoantigen-Major Histocompatibility Complex complex (Mutant RAS-MHC)

Mutant RAS neoantigens presented on Major Histocompatibility Complex (MHC) Class I and II molecules are pivotal targets for precision cancer immunotherapy [1]. RAS genes, including KRAS, NRAS, and HRAS, are among the most frequently mutated oncogenes in human cancers, with KRAS mutations appearing in approximately 90% of pancreatic and 40% of colorectal cancers [2]. These mutations result in unique peptide sequences that are processed and presented by MHC molecules on the tumor cell surface, distinguishing them from wild-type proteins [3]. T-cell receptors (TCRs) can specifically recognize these mutant RAS-MHC complexes as non-self, triggering a potent immune response against the tumor [4]. Therapeutic interventions such as TCR-engineered T-cell (TCR-T) therapies and neoantigen-based vaccines (e.g., ELI-002) are designed to exploit this recognition to achieve targeted tumor cell death [5]. The efficacy of these treatments is highly dependent on the patient's specific RAS mutation and their HLA (Human Leukocyte Antigen) genotype, which determines whether the mutant peptide can be successfully presented [6]. Challenges in this field include potential immune evasion through HLA downregulation and the risk of off-target toxicity if the TCR cross-reacts with similar self-peptides [7].

Other names

RAS neoantigenMutant RAS peptide-MHC complexKRAS neoepitopeRAS-HLA complexMutant RAS-MHC class I/IIRAS-derived peptide-MHC

T-cell receptor (TCR) mediated recognition of mutant RAS peptides presented by MHC molecules, leading to T-cell activation and targeted lysis of tumor cells.