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
