Mutant KRAS peptide-HLA complex (Mutant KRAS pHLA)

The mutant KRAS peptide-HLA complex is a tumor-specific neoantigen presented on the surface of cancer cells, consisting of a mutated KRAS fragment bound to specific Human Leukocyte Antigen (HLA) molecules like HLA-A*11:01 or HLA-C*08:02 (Tran et al., 2016; Sim et al., 2020). KRAS is a critical signaling protein that, when mutated at codon 12 (e.g., G12D, G12V), drives the uncontrolled proliferation of cells in pancreatic, colorectal, and lung cancers. These mutations generate unique amino acid sequences that are processed by the proteasome and loaded onto MHC Class I molecules for presentation to T cells. Because these mutant peptides are absent in normal tissues, the resulting peptide-HLA (pHLA) complex serves as an ideal target for precision immunotherapies, such as TCR-engineered T-cell (TCR-T) therapies and cancer vaccines (Pant et al., 2024). These therapies, including candidates like AFNT-211 and ELI-002, utilize the specificity of the T-cell receptor to recognize the pHLA complex and trigger a targeted cytotoxic immune response against the tumor (Bear et al., 2021). However, the effectiveness of targeting these complexes can be limited by tumor immune evasion mechanisms, such as the downregulation of HLA expression or the loss of the mutant KRAS allele.

Other names

KRAS neoantigenKRAS G12D/V peptide-MHC complexKRAS-HLA-A*11:01KRAS-HLA-C*08:02Mutant KRAS-MHC class I complex

T-cell receptor (TCR) mediated recognition leading to T-cell activation and directed cytotoxicity against tumor cells expressing the specific mutant KRAS peptide-HLA complex.