KRAS G12V-derived neoepitopes presented by HLA-DRB1*15:01 and HLA-DRB1*07:01 (KRAS G12V/HLA-DRB1*15:01/07:01)

KRAS G12V-derived neoepitopes presented by HLA-DRB1*15:01 and HLA-DRB1*07:01 are specific peptide-MHC class II complexes that serve as critical targets for cancer immunotherapy. The KRAS G12V mutation is a frequent oncogenic driver in pancreatic, colorectal, and lung cancers, resulting in a constitutively active protein that promotes malignant cell growth (Simanshu et al., 2017). When these mutated proteins are processed by antigen-presenting cells or tumor cells, the resulting neoantigenic peptides are loaded onto HLA-DRB1*15:01 or HLA-DRB1*07:01 molecules for presentation to CD4+ T cells (Tran et al., 2016). This presentation is vital for orchestrating a comprehensive immune response, as CD4+ T cells can provide essential help to CD8+ cytotoxic T cells or exert direct anti-tumor effects through cytokine secretion (June et al., 2018). Therapeutic interventions targeting these complexes, such as the ELI-002 vaccine or TCR-engineered T-cell therapies, aim to exploit this high specificity to selectively eliminate tumor cells while minimizing damage to healthy tissues (Pant et al., 2023). These therapies are particularly relevant for patients who carry the specific HLA alleles and the KRAS G12V mutation, making them a form of personalized precision medicine. However, challenges such as HLA downregulation and the requirement for specific patient HLA genotypes remain significant hurdles in the broad application of these therapies (Bear et al., 2020).

Other names

KRAS G12V/HLA-DRB1*15:01 complexKRAS G12V/HLA-DRB1*07:01 complexKRAS G12V MHC-II neoantigenKRAS G12V neoepitope

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD4+ T cells, leading to immune-mediated destruction of KRAS G12V-expressing tumor cells.