| Literature DB >> 29126850 |
James T Patterson1, Jason Isaacson2, Lisa Kerwin2, Ghazi Atassi2, Rohit Duggal2, Damien Bresson2, Tong Zhu2, Heyue Zhou2, Yanwen Fu2, Gunnar F Kaufmann3.
Abstract
Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity.Entities:
Keywords: Bioconjugation; Bispecific antibody; Click chemistry; Disulfide bridging; Fab
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Year: 2017 PMID： 29126850 DOI： 10.1016/j.bmcl.2017.09.065
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823