Off-target reactivity in clinical monoclonal antibodies - PubMed
5 hours ago
- #biologic drug development
- #antibody engineering
- #off-target reactivity
- Off-target reactivity is a significant risk in monoclonal antibodies (mAbs) used in clinical settings.
- A study evaluated 174 FDA-approved and clinical-stage antibodies against 6,172 human extracellular proteins using rapid extracellular antigen profiling (REAP).
- 28% of the antibodies showed at least one off-target interaction, highlighting a substantial burden of off-target reactivity.
- Off-target binding arises from antibody intrinsic properties and epitope mimicry, both within related protein families and across structurally unrelated proteins.
- The study identified new off-target interactions of tanezumab and engineered its variable domains to eliminate off-target binding while maintaining target affinity.
- The findings emphasize the importance of early specificity evaluation in biologic drug development to ensure safety and efficacy.