mutant KRAS neoantigen (predominantly KRAS G12V, HLA-restricted)

Class

engineered autologous TCR-T cell therapy

Pathway

TCR-transduced autologous T cells recognize HLA-presented mutant-KRAS peptide and kill matched tumor cells while sparing normal cells

KRAS is one of the most frequently mutated oncogenes in human cancer, and mutations such as G12V lock the KRAS protein in an active, growth-promoting state. Although KRAS itself sits inside the cell, fragments of the mutant protein are naturally processed and displayed on the cell surface bound to HLA molecules, creating a distinctive marker recognizable to the immune system called a neoantigen. This engineered cell therapy works by removing T cells from a patient, equipping them with a T-cell receptor (TCR) engineered to recognize this specific HLA-mutant-KRAS peptide combination, expanding the modified cells, and reinfusing them so they can seek out and destroy tumor cells displaying that exact signal. Because the target sequence differs from the normal KRAS protein by only a few amino acids, the approach aims to attack tumor cells selectively while leaving normal tissue, which expresses only wild-type KRAS, largely untouched. This strategy matters broadly for cancers driven by KRAS mutations, including pancreatic, colorectal, and lung tumors, and more generally demonstrates how TCR-based cell therapies can reach intracellular oncogenic drivers that antibody-based or CAR-T approaches cannot directly access, since those depend on antigens already present on the cell surface.