TCRm HLA peptide purification

Clinically, Natural peptides recognized by affinity-enhanced TCRs lead to severe off-target toxicity in early clinical studies, requiring thorough screening for such off-targeting on healthy cells. While Alithea has collected an extensive quantitative dataset of HLA peptides in healthy tissue  to support the investigation of the safety of TCR or TCRm antibodies, [LINK TO OFF-TARGET TOX PREDICION] these studies are based on in-silico prediction of off-target binding.

A more physiologic experiment is the purification of HLA peptide-complexes with these soluble binders in a process published by Marrer-Berger, M., et al. (Nature Communications, 15, 3271). In such procedures, HLA-peptide complexes are purified with specific affinity resin similar to the general protocol of HLA peptide purification with widely used W6/32 antibody from cell or tissue lysate. It is possible to conjugate TCR mimic antibodies and soluble TCRs to such solid support and to compare elution profile between conditions to identify off-targets by mass spectrometry.

If you are interested TCRm HLA peptide purification for physiological off target toxicity screening, please contact us