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Kirsten rat sarcoma viral oncogene homolog G12V peptide–HLA-A*11:01 complex (KRAS G12V–HLA-A*11 complex)

Target
KRAS G12V–HLA-A*11 complex
Molecular classification
Protein complex, Neoantigen presentation complex, Major histocompatibility complex (MHC) class I–bound neoantigen, Oncogenic peptide–MHC complex
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Overview

The Kirsten rat sarcoma viral oncogene homolog G12V peptide–HLA-A*11:01 complex is a tumor-specific antigenic complex formed when the cancer-associated KRAS G12V mutant peptide is presented on the cell surface by the HLA-A*11:01 major histocompatibility complex class I molecule[1][5]. This complex serves as a neoantigen, uniquely present on tumor cells harboring the KRAS G12V mutation and the HLA-A*11:01 allele, enabling highly specific recognition by engineered T cell receptors[1][5]. As such, it is an actionable target for next-generation immunotherapies, including TCR-engineered T cell therapies and T cell engager molecules, offering potent anti-cancer effects with the potential for precision and safety[1][5]. The parent protein, KRAS, is a small GTPase that drives cell proliferation and survival in many cancers, and mutations at codon 12 (such as G12V) are among the most frequent oncogenic drivers in solid tumors[1][2][3][4][5]. Notes on structure and naming: - KRAS G12V refers to a glycine-to-valine substitution at position 12 in the KRAS protein. - HLA-A*11:01 is a specific human leukocyte antigen required for peptide presentation and TCR recognition. - The complex is what T cell receptors recognize in the context of immunotherapies; other drugs typically target KRAS protein itself. - This is a validated and specific immunological target, but how commonly it is referenced in drug databases as a “target” may vary—the canonical “parent” is Kirsten rat sarcoma viral oncogene homolog G12V (KRAS G12V). If more generalized, the canonical entry should be: - Canonical full name: Kirsten rat sarcoma viral oncogene homolog G12V - Canonical abbreviation: KRAS G12V - (The HLA restriction is important for immunotherapies, but the “target” for standard annotation is usually the mutant protein.)

Other names
KRAS G12V–HLA-A*11:01 complexKRAS G12V neoantigen–HLA-A11 complexKRAS G12V peptide–HLA-A*11:01
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Mechanism of action

Adoptive T cell therapies (TCR-T): Engineered T cells express TCRs that specifically recognize the KRAS G12V peptide presented by HLA-A*11:01 on tumor cells, leading to targeted cytotoxicity and cytokine release against cancer cells[1][5].

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Biological functions

Antigen presentation (via HLA-A*11)Immune response activation (specific T cell recognition)Tumor-specific immune recognitionCell proliferation (due to KRAS function)Signal transduction (parent protein)
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Disease associations

Cancer (especially pancreatic, colorectal, lung adenocarcinoma, urogenital cancers)Biomarker of poor prognosis, driver mutation
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Safety considerations

On-target, off-tumor toxicity: Risk of TCR therapies accidentally targeting normal tissues that present similar peptidesCytokine release syndrome (CRS) (general risk in T cell–engaging therapies)T cell exhaustion or suboptimal persistenceTumor escape via antigen loss or HLA downregulation
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Interacting drugs

Investigational T cell receptor (TCR)-engineered therapies (e.g., adoptive T cell therapy, TCR-TCEs, such as MDG3010)

1 more in the full profile.

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Biomarkers

KRAS G12V mutation (tumor genotyping)HLA-A*11:01 allele status (required for this antigen presentation)

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