Dual Function pH Responsive Bispecific Antibodies for Tumor Targeting and Antigen Depletion in Plasma.

ABSTRACT: Shedding of membrane-bound cell surface proteins, where the extracellular domain is released and found in the circulation is a common phenomenon. A prominent example is CEACAM5 (CEA, CD66e), where the shed domain plays a pivotal role in tumor progression and metastasis. For treatment of solid tumors, the presence of the tumor-specific antigen in the plasma can be problematic since tumor-specific antibodies might be intercepted by the soluble antigen before invading their desired tumor target area. To overcome this problem, we developed a generic procedure to generate bispecific antibodies, where one arm binds the antigen in a pH-dependent manner thereby enhancing antigen clearance upon endosomal uptake, while the other arm is able to target tumor cells pH-independently. This was achieved b

SUBMITTER: Bogen JP 

PROVIDER: S-EPMC6697062 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature