Addressing soluble target interference in the development of a functional assay for the detection of neutralizing antibodies against a BCMA-CD3 bispecific antibody

Current Analytical Strategies for Antibody–Drug Conjugates in Biomatrices

“…A drug target, when present at sufficiently high concentrations in the bloodstream, may interfere with the performance of ADA and NAb assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results [ 58 ]. Related mitigation approaches include the use of anti-target antibodies [ 59 ], soluble versions of the receptors [ 60 ], target-binding proteins [ 61 ], lectins [ 62 ], and solid-phase removal of targets. For example, Wang et al used polyclonal anti-soluble B-cell maturation antigen (sBCMA) antibodies as scavengers to deplete sBCMA at a concentration four times greater than the median level of this tumor-associated antigen observed in the multiple myeloma patient population, thereby mitigating sBCMA interference in the related functional assay for the detection of neutralizing antibodies against a BCMA-CD3 bispecific antibody [ 59 ].…”

“…Related mitigation approaches include the use of anti-target antibodies [ 59 ], soluble versions of the receptors [ 60 ], target-binding proteins [ 61 ], lectins [ 62 ], and solid-phase removal of targets. For example, Wang et al used polyclonal anti-soluble B-cell maturation antigen (sBCMA) antibodies as scavengers to deplete sBCMA at a concentration four times greater than the median level of this tumor-associated antigen observed in the multiple myeloma patient population, thereby mitigating sBCMA interference in the related functional assay for the detection of neutralizing antibodies against a BCMA-CD3 bispecific antibody [ 59 ]. For another example, Dengler et al managed to overcome the interference of prior checkpoint inhibitor with the immunogenicity assays by using antibodies specific to pembrolizumab or nivolumab [ 63 ].…”