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The KRAS G12V peptide-MHC complex-specific CD8+ T cell receptor (TCR) is a type of engineered or naturally occurring TCR that specifically recognizes the mutant KRAS G12V neoantigen presented by certain human leukocyte antigen (HLA) class I molecules on tumor cells. This target is of high interest for cancer immunotherapy, particularly in solid tumors such as pancreatic and colorectal cancers, where the KRAS G12V mutation is prevalent. The receptor binds specifically to the mutant KRAS G12V peptide presented by compatible MHC molecules on tumor cells. Upon recognition, it triggers cytotoxic activity leading to targeted killing of cancer cells expressing this neoantigen. These TCRs show exquisite specificity for mutated over wild-type KRAS peptides, minimizing off-target effects against normal tissues. Adoptive transfer of engineered or selected mKRAS-G12V-specific CD8+ T cells has demonstrated potent anti-tumor activity in preclinical models and early clinical studies. Such therapies are being developed as personalized immunotherapies for patients whose tumors harbor the relevant mutation and HLA type.
TCR binding to KRAS G12V-MHC complex leading to T cell activation and target cell lysis.
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