Off-target toxicity due to antibody cross-reactivity can present a major problem in drug development. Early knowledge of a potential off-target interaction can allow for strategies to manage and mitigate risks. It could even signal a halt on development of a drug prior to costly clinical studies that may fail to achieve endpoints or could even endanger the safety of patients or other trial participants. Tissue cross-reactivity (TCR) is a standard tool in safety assessment that can indicate a potential off-target issue. However, the technique does not reveal the identity of any specific off-target receptor or point to a potential mechanism of action that would help with evaluating the potential threat that the antibody cross-reactivity posed.
Retrogenix’s cell microarray technology was originally developed to identify the primary receptors that bind specifically to ligands of interest, ranging from small molecules, peptide and protein ligands and antibodies right through to complex ligands such as engineered cell lines and viruses. More recently, this sensitive technology has become widely adopted across the pharmaceutical industry for IND-enabling cross-reactivity screening of candidate biotherapeutics for potential off-target binding as part of their pre-clinical safety assessment. Here we present details of a typical cell microarray antibody cross-reactivity screen, which was followed by flow cytometry analysis to validate/invalidate observed interactions. This provided highly valuable insight into the receptor binding profile of an antibody candidate.