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The aim is to identify a pMHC antigen related to KRAS amplification that can be targeted for T cell therapies.

KRAS Amplification Generates Targetable pMHC Antigen for T Cell Engager Therapy

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The aim is to identify a pMHC antigen related to KRAS amplification that can be targeted for T cell therapies.
Utilized peptide prediction and immunopeptidomics to identify KRAS-specific antigens.
Conducted quantitative analyses to determine antigen expression in KRAS-amplified versus non-amplified cell lines.
Engineered A*02:01-negative lines for comparative assessments.
Screened human antibody libraries for TCR-mimicking antibodies.
Identified kAMP.A2 as a specific antigen present in KRAS-amplified tumors.
Measured kAMP.A2 expression levels reaching ∼4,000 copies per cell after treatment with KRAS inhibitors.
Demonstrated potent cytotoxicity of engineered TCEs in KRAS-amplified models (EC50 values ranging from 150 pM to 1.1 nM).
Developed the antibody PK313, showing high specificity and affinity for kAMP.A2.

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Identifies a targetable pMHC antigen in KRAS-amplified tumors, suggesting a novel therapeutic strategy for KRAS inhibitor resistance.

Maso et al. (2026) studied this question.

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