Logic-gated antibody pairs that selectively act on cells co-expressing two antigens.

ABSTRACT: The use of therapeutic monoclonal antibodies is constrained because single antigen targets often do not provide sufficient selectivity to distinguish diseased from healthy tissues. We present HexElect^®, an approach to enhance the functional selectivity of therapeutic antibodies by making their activity dependent on clustering after binding to two different antigens expressed on the same target cell. lmmunoglobulin G (lgG)-mediated clustering of membrane receptors naturally occurs on cell surfaces to trigger complement- or cell-mediated effector functions or to initiate intracellular signaling. We engineer the Fc domains of two different lgG antibodies to suppress their individual homo-oligomerization while promoting their pairwise hetero-oligomerization after binding co-expresse

SUBMITTER: Oostindie SC 

PROVIDER: S-EPMC9546771 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature