Manipulation of Cell-Type Selective Antibody Internalization by a Guide-Effector Bispecific Design.

ABSTRACT: Cell-type-specific intracellular payload delivery is desired for antibody-based-targeted therapy development. However, tumor-specific internalizing antigens are rare to find, and even rarer for those that are expressed at uniformly high levels. We constructed a bispecific antibody that is composed of a rapidly internalizing antibody binding to a tumor-associated antigen, ephrin receptor A2 (EphA2), and a noninternalizing antibody binding to a highly expressed tumor-associated antigen, activated leukocyte cell adhesion molecule (ALCAM). We found that the overall internalization property of the bispecific is profoundly impacted by the relative surface expression level (antigen density ratio) of EphA2 versus ALCAM. When the EphA2-to-ALCAM ratio is greater than a threshold level (1:5), the amo

SUBMITTER: Lee NK 

PROVIDER: S-EPMC6548581 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature