Identification of fully human TCR-mimic antibodies targeting the KRAS G12V/HLA complex generated in HLA-transgenic RenMab mice

Identification of fully human TCR-mimic antibodies targeting the KRAS G12V/HLA complex generated in HLA-transgenic RenMab mice

SUMMARY

  • We identified TCR-mimic antibodies specific for KRAS G12V residues 7-16 complexed with HLA-A03 or HLA-A11.
  • Both anti-KRAS G12V/HLA-A11 and anti-KRAS G12V/HLA-A03 antibodies showed abundant germline gene diversity and high affinity.
  • Anti-KRAS G12V/HLA-A03 antibodies did not cross-bind HLA-A11 overexpressing cells loaded with KRAS mutant or wild-type peptides, or HLA-A03 overexpressing cells loaded with off-target peptides.
  • The residue V6 of KRAS G12V was required for antibody binding according to the alanine scan assay. Cytotoxicity assays demonstrated specificity of the bispecific anti-KRAS G12V/HLA-A03 x CD3 T cell engager for KRAS G12V+/HLA-A0301+ cells.

Used in the study: TCR-Mimic Antibody Platform

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