Development of a T-cell receptor mimic antibody targeting a novel Wilms tumor 1-derived peptide and analysis of its specificity.

Wilms tumor 1 (WT1) is an intracellular tumor-associated antigen that remains inaccessible to antibodies. Recently, T-cell receptor (TCR) mimic antibodies (TCRm-Abs), which recognize peptides loaded on human leukocyte antigen (HLA) with higher specificity and affinity than TCR, have been developed as a new antibody class that can target intracellular antigens. To expand the therapeutic targets in tumors with WT1, we developed TCRm-Abs targeting a novel HLA-A*02:01-restricted peptide, WT1C (ALLPAVPSL), and validated their specificity using multiple techniques.

High throughput development of TCR-mimic antibody that targets survivin-2B/HLA-A*A24 and its application in a bispecific T-cell engager.

Intracellular tumor-associated antigens are targeted by antibodies known as T-cell receptor mimic antibodies (TCRm-Abs), which recognize T-cell epitopes with better stabilities and higher affinities than T-cell receptors. However, TCRm-Abs have been proven difficult to produce using conventional techniques. Here, we developed TCRm-Abs that recognize the survivin-2B-derived nonamer peptide, AYACNTSTL (SV2B), presented on HLA-A*24 (SV2B/HLA-A*24) from immunized mice by using a fluorescence-activated cell sorting-based antigen-specific plasma cells isolation method combined with a high-throughput single-cell-based immunoglobulin-gene-cloning technology.