Human cell microarray technology is a powerful and highly validated method for off-target screening of biotherapeutics. As such, it is now the standard tool for lead selection and for safety assessment, providing supportive data for IND submissions. Many molecule types can be screened, including mono- and bi-specific antibodies, ScFvs, ADCs, proteins, peptides, and whole CAR T cells. The high success rates and low false positive rates result from the expression of a large, high quality library of full-length human plasma membrane proteins in the context of human cells.
Off-target binding to secreted proteins also has the potential to cause clinical toxicity or alter the pharmacokinetic profile of biotherapeutics in development. Here we describe the adaptation of the cell microarray technology – beyond the plasma membrane proteome – to screen for interactions with proteins that are usually secreted from the cell.