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This research aims to identify a targetable pMHC antigen in KRAS-amplified tumors for T cell engager therapy.

Abstract PR011: KRAS amplification creates a targetable pMHC antigen for T cell engager therapy to overcome KRAS inhibitor resistance

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This research aims to identify a targetable pMHC antigen in KRAS-amplified tumors for T cell engager therapy.
Identified the pMHC antigen pKA-A2 through peptide prediction and immunopeptidomics.
Quantitatively assessed pKA-A2 levels in KRAS-amplified and non-amplified cell lines.
Engineered HLA-A*02:01-negative cell lines for testing the specificity of the T cell engager.
Analyzed the cytotoxic effects of PK313 on KRAS-amplified cell lines with and without KRAS inhibitors.
pKA-A2 was significantly more abundant (up to ∼4,000 copies-per-cell) in KRAS-amplified lines versus undetectable in non-amplified lines.
PK313 demonstrated strong cytotoxicity against KRAS-amplified cells with low EC50 values.
Engineered PK313 showed high specificity for pKA-A2 with minimal off-target effects.

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Targeting KRAS amplification improves therapeutic strategies in HLA-A*02:01 patients, enhancing treatment outcomes.

Maso et al. (2026) studied this question.

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