KRAS G12D presented on HLA-A*11:01

Class

CRISPR-engineered autologous TCR-T cell therapy

Pathway

Engineered T-cell receptor recognizes mutant KRAS G12D neoantigen peptide presented by HLA-A*11:01 on tumor cells

KRAS is a signaling protein that normally switches on and off to control cell growth. In several difficult-to-treat cancers, including pancreatic and colorectal tumors, a mutation called G12D locks it into a permanently active state, driving uncontrolled proliferation. This mutation also produces a short altered peptide fragment that some tumor cells display on their surface, bound to a specific class I human leukocyte antigen (HLA) molecule, HLA-A*11:01. This peptide-HLA combination is a neoantigen, a marker unique to cancer cells because it arises directly from the mutation and is absent from healthy tissue. This mechanism uses an engineered T-cell receptor (TCR) designed to recognize that exact complex. T cells collected from a patient are modified using CRISPR gene-editing to carry this engineered receptor, then expanded outside the body and reinfused. Once returned, these TCR-engineered T cells can identify and destroy tumor cells displaying the mutant peptide-HLA complex while sparing normal cells lacking it. Because both the specific mutation and the specific HLA type must be present in a given patient, this strategy applies only to a defined subset of tumors, but it offers precise targeting of a cancer-driving alteration rather than a generic tumor marker.