TCR-like antibodies are an emerging class of therapeutics as they allow the targeting of intracellular proteins which are displayed as peptides by MHC proteins on the cell surface. Thus, a novel epitope space of cancer targets can be addressed that had been undruggable with conventional antibodies so far. However, the potential risk for off-target binding of TCRs and TCR-like antibodies remains challenging and needs to be addressed

Here, we present YUMAB’s natural human pHLA display library and demonstrate how it can be used to select and screen for highly target specific antibodies using a library vs library approach. The resulting antibodies from this novel discovery platform are highly diverse and show superior binding characteristics as compared to reference antibodies. When tested in various T-cell engager formats, using YUMAB’s proprietary CD3-specific VHH, the antibodies showed efficient and specific target cell killing.

Key Topics:

• Safety assessment of TCR and TCR-like antibodies remains challenging and requires robust ex-vivo model systems.


• YUMAB presents a novel CHO-display library that closely mimics the natural human peptide:HLA (pHLA) repertoire.


• This platform enables the selection and identification of human antibody candidates with highly specific binding profiles that outperform current gold standards.


• YUMAB further demonstrates that these pHLA antibodies can be converted easily into bispecific T-cell engagers using YUMAB's proprietary CD3-specific VHH antibodies, which induce potent T-cell activation and target cell killing.