A dual computational and experimental strategy to enhance TSLP antibody affinity for improved asthma treatment

Thymic stromal lymphopoietin is a key cytokine involved in the pathogenesis of asthma and other allergic diseases. Targeting TSLP and its signaling pathways is increasingly recognized as an effective strategy for asthma treatment. This study focused on enhancing the affinity of the T6 antibody, which specifically targets TSLP, by integrating computational and experimental methods. The initial affinity of the T6 antibody for TSLP was lower than the benchmark antibody AMG157. To improve this, we utilized alanine scanning, molecular docking, and computational tools including mCSM-PPI2 and GEO-PPI to identify critical amino acid residues for site-directed mutagenesis. Subsequent mutations and experimental validations resulted in an antibody with significantly enhanced blocking capacity against TSLP. Our findings demonstrate the potential of computer-assisted techniques in expediting antibody affinity maturation, thereby reducing both the time and cost of experiments. The integration of computational methods with experimental approaches holds great promise for the development of targeted therapeutic antibodies for TSLP-related diseases. Computer-assisted affinity maturation significantly reduces experimental time and lowers research costs. Targeting thymic stromal lymphopoietin and its signaling pathways with specific antibody drugs is widely recognized as an effective strategy for treating asthma. In our study, we successfully identified a TSLP-targeting antibody from the fully synthetic human phage antibody libraries. We integrated computer-assisted methods to enhance the antibody's affinity. These techniques enabled efficient prediction of critical amino acid residues, guiding targeted mutagenesis experiments. By combining computer-assisted approaches with experimental methods, we have successfully developed a mature method for enhancing antibody affinity. Through this research, we have obtained an antibody with high affinity for TSLP, providing a new avenue for treating asthma and other TSLP-related diseases. The computer-assisted affinity maturation strategy brings hope for speeding up the drug development process.