KRAS-derived peptide-HLA-A*02:01 complex (KRAS-HLA-A*02:01)

The KRAS-derived peptide-HLA-A*02:01 complex is a tumor-specific neoantigen target composed of a mutant KRAS peptide (such as G12V or G12D) bound to the human leukocyte antigen (HLA) allele A*02:01 (Source: Science Advances, 2024). KRAS is a membrane-bound GTPase that, when mutated, drives oncogenesis in various cancers, including pancreatic, colorectal, and lung adenocarcinomas (Source: NIH, 2021). Because KRAS is an intracellular protein, its mutant forms are processed by the proteasome and presented on the cell surface as peptide-MHC complexes, making them accessible to the adaptive immune system (Source: Nature Communications, 2021). While some research has highlighted the low presentation levels of these complexes on HLA-A*02:01, recent advances have identified spliced epitopes and developed high-affinity TCR-mimic (TCRm) antibodies and TCR-engineered T-cells to target them (Source: Frontiers in Immunology, 2021). Therapeutic strategies include TCR-T therapies like AFNT-211, TCRm chimeric antigen receptors (CARs), and peptide vaccines such as ELI-002 (Source: Affini-T Therapeutics, 2023; Elicio Therapeutics, 2024). These therapies aim to selectively eliminate cancer cells while sparing healthy tissues that lack the specific mutation or the restricting HLA allele. However, challenges such as low peptide-HLA density and potential cross-reactivity with wild-type proteins remain significant hurdles in clinical development (Source: NIH, 2021).

Other names

KRAS neoantigen-HLA-A*02:01 complexKRAS G12V-HLA-A*02:01KRAS G12D-HLA-A*02:01KRAS-pHLA-A*02:01Mutant KRAS-HLA-A*02:01 complex

Recognition of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-mimic antibodies, leading to T-cell activation, secretion of pro-inflammatory cytokines like IFN-gamma, and direct cytotoxic lysis of tumor cells.