The Molecular Landscape of the Immune Response Following Treatment with Biologics

Monoclonal antibodies (mAb) govern the biologics drug market with tremendous impact as clinical therapeutics. However, the repeated administration of mAbs may induce a strong immune response manifested in the formation of anti-drug antibodies (ADA) that reduces drug efficacy. However, little is known about the molecular landscape of ADA. Here, utilizing a newly developed quantitative bio-immunoassay we found that ADA concentration can exceed the extreme concentrations of 1 mg/ml with wide range of neutralization capacity. More interestingly, our data suggests that there is a preferential usage of the l light chain in the neutralizing ADA compartment. Next, utilizing advanced omics tools we found that TNFa antagonists administration results in a vaccine like response and ADA formation is governed by and extrafollicular T cell independent immune response. Our developed bio-immunoassay coupled with the insights regarding the nature of the immune response can be readily leveraged for mAb immunogenicity assessment and assist clinicians in purposing better therapeutic intervention strategies.