Human leukocyte antigen A*11:01–KRAS G12D peptide complex (HLA-A*11:01–KRAS G12D)

The Human leukocyte antigen A*11:01–KRAS G12D peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical neoantigen target in cancer immunotherapy (aacrjournals.org, 2025). It consists of a mutant KRAS peptide, specifically the G12D mutation where glycine is replaced by aspartic acid at position 12, presented by the human leukocyte antigen (HLA) allele A*11:01 (nih.gov, 2022). This complex is highly prevalent in several aggressive malignancies, including pancreatic, colorectal, and lung cancers, where KRAS G12D is a dominant oncogenic driver (aacrjournals.org, 2025). Because the mutation is absent in normal tissues, the complex provides a highly specific target for T-cell receptor (TCR)-engineered T-cell therapies and TCR-mimic antibodies (frontiersin.org, 2025). Therapeutic strategies aim to redirect the immune system to recognize and eliminate tumor cells presenting this specific pMHC, often utilizing affinity-enhanced TCRs to overcome the typically low levels of neoantigen presentation on the cell surface (nih.gov, 2022). Clinical candidates like AZD0240 and NW-301D are currently being evaluated in phase 1 trials to treat patients whose tumors express this specific neoantigen (clinicaltrials.gov, 2024; aacrjournals.org, 2025). A significant challenge in targeting this complex is ensuring high specificity to avoid cross-reactivity with wild-type KRAS or other self-peptides like RAB7B (nih.gov, 2025). Overall, this target represents a promising avenue for personalized medicine in patients with KRAS-mutant solid tumors (frontiersin.org, 2025).

Other names

KRAS G12D/HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12D neoantigenKRAS G12D-10/HLA-A*11:01pMHC complexHLA-A*11:01-KRAS G12D

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex followed by T-cell activation and cytotoxic lysis of the target tumor cell.