Mutant RAS neoantigen-expressing tumor cell

Mutant RAS neoantigen-expressing tumor cells are malignant cells characterized by somatic mutations in the RAS gene family (KRAS, NRAS, or HRAS) that result in the presentation of unique, tumor-specific peptides on the cell surface via Major Histocompatibility Complex (MHC) molecules [1]. These mutations, most commonly occurring at positions G12, G13, or Q61, drive constitutive proliferative signaling and are hallmark features of aggressive cancers such as pancreatic, colorectal, and lung adenocarcinomas [2]. Because these mutant sequences are not present in the normal human proteome, they function as high-quality neoantigens that can be recognized by the immune system as foreign [3]. Therapeutic interventions targeting these cells include adoptive T-cell therapies (TCR-T), which engineer patient T cells to express receptors specific for the RAS peptide-MHC complex, and neoantigen vaccines designed to prime endogenous T-cell responses [4]. While these therapies offer high specificity and the potential to treat historically undruggable RAS variants, their efficacy can be limited by tumor-mediated immune evasion, such as the loss of HLA expression or the development of a suppressive tumor microenvironment [1,3]. Citations: [1] Leidner, R., et al. (2022). NEJM. [2] Simanshu, D. K., et al. (2017). Cell. [3] Pant, S., et al. (2023). Nature Medicine. [4] Waters, A. M., & Der, C. J. (2018). Cold Spring Harb Perspect Med.

Other names

KRAS-mutant tumor cellRAS neoantigen-positive cellMutant RAS pMHC-bearing cellmRAS-expressing tumor cell

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