KRAS G12D-derived peptide presented by HLA-C*08:02 (KRAS G12D/HLA-C*08:02)

The KRAS G12D-derived peptide presented by HLA-C*08:02 is a specific neoantigen complex formed when the mutated KRAS protein is processed and displayed on the cell surface. This complex consists of a 9- or 10-amino acid peptide containing the G12D mutation bound to the cleft of the HLA-C*08:02 MHC Class I molecule (Tran et al., 2016, N Engl J Med). It is highly tumor-specific because the G12D mutation is a common oncogenic driver in pancreatic, colorectal, and lung cancers but is not found in healthy cells (Sim et al., 2020, Cancer Immunol Res). The complex serves as a target for T-cell receptor (TCR) based therapies, which utilize the immune system's ability to recognize intracellular mutations presented on the surface. Clinical proof-of-concept was established in a landmark study where a patient with metastatic colorectal cancer experienced significant tumor regression after receiving TILs specific to this complex (Tran et al., 2016). Ongoing research aims to develop off-the-shelf TCR-T therapies and bispecific molecules that can exploit this target to provide precision immunotherapy for patients harboring both the specific mutation and the HLA genotype.

Other names

KRAS G12D:HLA-C*08:02 complexHLA-C*08:02-restricted KRAS G12D neoantigenG12D-9 peptide/HLA-C*08:02KRAS G12D neoepitope

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like molecules to induce T-cell mediated lysis of tumor cells.