Modeling bispecific monoclonal antibody interaction with two cell membrane targets indicates the importance of surface diffusion.

ABSTRACT: We have developed a mathematical framework for describing a bispecific monoclonal antibody interaction with two independent membrane-bound targets that are expressed on the same cell surface. The bispecific antibody in solution binds either of the two targets first, and then cross-links with the second one while on the cell surface, subject to rate-limiting lateral diffusion step within the lifetime of the monovalently engaged antibody-antigen complex. At experimental densities, only a small fraction of the free targets is expected to lie within the reach of the antibody binding sites at any time. Using ordinary differential equation and Monte Carlo simulation-based models, we validated this approach against an independently published anti-CD4/CD70 DuetMab experimental data set. As a resul

SUBMITTER: Sengers BG 

PROVIDER: S-EPMC4968105 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature