Peptide Mimotope Optimization
Zolbetuximab (IMAB362) is a chimeric monoclonal antibody that showed promising results in the treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma and is currently evaluated in phase III studies (Sahin et al. Ann. Oncol. 2021. PMID: 33610734).
Peptidic mimotopes for the ELISA-based detection of IMAB362 in biological samples were developed. Initial hits were identified using phage display and optimized with the help of structure-activity relationship analysis on peptide microarrays. The optimized peptides showed binding constants in the low nanomolar to picomolar range - an improvement by a factor of up to 30 compared to the initial hits. The best mimotope (apparent KD = 0.15 nM) was successfully used for the ELISA-based quantification of IMAB362 in samples from a mouse pharmacokinetic study.