Characterization of a novel therapeutic antibody targeting peptide/HLA-E

Abstract T-cell receptor mimic antibodies (TCRm) have become an attractive therapeutic modality group as they allow for the targeting of intracellular proteins presented by HLA, which may a large potential new targets. However, polymorphic nature classical HLA class I and findings downregulation in cancer cells might limit use these agents treatment. An alternative approach would be to target peptides HLA-E, highly monomorphic molecule often found upregulated cells. Thus, we aimed generate TCRm against HLA-E presenting leader sequence peptide from HLA-G since both HLAs are expressed multiple types. antibody was identified naïve human phage library further affinity matured using yeast display. The final clone, ABX-001, had constant (K D) 7.9nM. Specificity studies peptide-loaded tumor cell lines showed that ABX-001 only bound when were present. Extensive profiling done on immune also confirm did not bind ABX-001. Finally, assessed its ability direct killing target-positive lines. We observed cytotoxicity CD8 +T enhanced with addition ABX-001-CD3 T engager. can act checkpoint inhibitor blocking interaction NKG2A experiments NK These data indicate effectively peptide/HLA-E highlights applications