KRAS G12V peptide presented by HLA-A*03:01

Class

T-cell engager (bispecific TCE)

Pathway

Redirects T cells against HLA-A*03:01-restricted mutant KRAS G12V peptide displayed on tumor cell surface

This target combines two elements: a specific oncogenic mutation in the KRAS protein (G12V, a single amino-acid substitution that locks the protein in a growth-signaling active state) and the human leukocyte antigen (HLA) system that displays fragments of internal proteins on the cell surface. Mutant KRAS is normally invisible to antibody-based drugs because it resides inside the cell, but when a peptide fragment derived from G12V is loaded onto HLA-A*03:01 and displayed on the tumor cell surface, it becomes a marker that immune cells can, in principle, recognize. A T-cell engager exploits this by binding simultaneously to the peptide-HLA complex on the tumor cell and to a receptor component on a T cell, physically bridging the two and prompting the T cell to kill the tumor cell. This approach matters because KRAS mutations, including G12V, drive a substantial share of solid tumors, particularly in the pancreas, colon, and lung, and have historically been difficult to target directly. Peptide-HLA-directed engagers extend druggability to intracellular oncoproteins by converting them into surface-visible immune targets, though efficacy depends on the tumor consistently presenting the mutant peptide and on the patient carrying the required HLA allele.