Broadening and Enhancing Functions of Antibodies by Self-Assembling Multimerization at Cell Surface.

ABSTRACT: Monoclonal antibody therapy has offered treatment benefits. Nonetheless, a lack of efficacy still exists, partially because monovalent binding of antibodies to specific receptors fails to translate into an active response. Here, we report a pretargeting-postassembly approach that exploits the selective Watson-Crick base pairing properties of oligonucleotides and multivalently tethers receptor-prebound antibodies to albumin at the cell surface. We demonstrate that this two-step self-assembling strategy allows sequential actions of receptor binding and clustering that broadens and strengthens the functions of antibodies. We show that anti-CD20 obinutuzumab (OBN) modified with one morpholino oligonucleotide (OBN-MORF1) maintains the feature of naked OBN antibody upon CD20 binding, and results

SUBMITTER: Li L 

PROVIDER: S-EPMC6812323 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature