Kirsten rat sarcoma virus oncogene homolog (KRAS) G12D peptide presented by Human Leukocyte Antigen (HLA) A*11:01 (KRAS G12D/HLA-A*11:01)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) G12D peptide presented by Human Leukocyte Antigen (HLA) A*11:01 is a tumor-specific neoantigen complex. KRAS is a small GTPase that acts as a molecular switch in signaling pathways like MAPK and PI3K, regulating cell growth and survival, and the G12D mutation is a frequent oncogenic driver in pancreatic, colorectal, and lung cancers (Simanshu et al., 2017, Cell). In cells harboring this mutation, the mutated KRAS protein is processed by the proteasome into peptides, such as the 9-mer VVVGADGVG, which are then loaded onto HLA-A*11:01 molecules and displayed on the cell surface (Leidner et al., 2022, NEJM). This specific peptide-MHC complex serves as a highly selective target for immunotherapies, such as TCR-engineered T cells (TCR-T) and neoantigen vaccines, because it is absent on healthy cells. Therapeutic strategies aim to harness the immune system to recognize this complex and selectively eliminate malignant cells while sparing normal tissue (Affini-T Therapeutics, 2024). Clinical trials have demonstrated that targeting this complex can lead to significant tumor regression in patients with advanced pancreatic cancer (Leidner et al., 2022, NEJM).

Other names

KRAS G12D neoantigenHLA-A*11:01-restricted KRAS G12DKRAS G12D 9-mer peptide-HLA-A*11:01 complexVVVGADGVG-HLA-A*11:01

T-cell receptor (TCR) mediated recognition and cytotoxic killing of tumor cells.