Mutant KRAS peptide–HLA complex

The Mutant KRAS peptide–HLA complex is a cell-surface molecular complex formed when a peptide fragment derived from a mutant KRAS protein (most commonly G12V or G12D mutations) is presented by a human leukocyte antigen class I (HLA-I) molecule, such as HLA-A*11:01 or HLA-A*03:01[1][2][5][6]. This complex represents a cancer-specific neoantigen that can be recognized selectively by T cell receptors (TCRs), enabling it to be therapeutically targeted in adoptive T-cell therapies and other immunotherapeutic modalities. Its molecular structure enables precise targeting by engineered immune receptors with high specificity for the mutant peptide-HLA context while minimizing cross-recognition of normal, wild-type peptides. As a target, it is central to next-generation personalized immunotherapies for cancers harboring mutant KRAS, such as pancreatic and lung adenocarcinomas[2][4][5]. However, efficacy and safety concerns are influenced by HLA polymorphism, the risk of off-tumor, on-target effects, and immune escape mechanisms.

Other names

Mutant KRAS–HLA complexKRAS G12V peptide–HLA complexMutant KRAS neoantigen–HLA complexKRAS mutant peptide–HLA

Targeted by TCR-engineered therapies: T cells or immune effectors recognize and kill tumor cells presenting mutant KRAS peptide–HLA complexes[2][4][5]. Recognition by high-affinity TCRs stimulates cytotoxic T cell killing of tumor cells[2][5]. Engaged by bispecific agents (ImmTAC, BiTE) to redirect immune effectors against tumor cells[4].