5O4O

HER3 in complex with Fab MF3178

Summary for 5O4O

• Entry DOI: 10.2210/pdb5o4o/pdb
• Descriptor: MF3178 FAB light chain, MF3178 FAB heavy chain, Receptor tyrosine-protein kinase erbB-3, ... (5 entities in total)
• Functional Keywords: her3 ectodomain, complex, fab, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 123600.23

Authors

De Nardis, C.,Gros, P. (deposition date: 2017-05-30, release date: 2018-05-16, Last modification date: 2024-10-23)

Primary citation

Geuijen, C.A.W.,De Nardis, C.,Maussang, D.,Rovers, E.,Gallenne, T.,Hendriks, L.J.A.,Visser, T.,Nijhuis, R.,Logtenberg, T.,de Kruif, J.,Gros, P.,Throsby, M.
Unbiased Combinatorial Screening Identifies a Bispecific IgG1 that Potently Inhibits HER3 Signaling via HER2-Guided Ligand Blockade.
Cancer Cell, 33:922-936.e10, 2018

PubMed Abstract: HER2-driven cancers require phosphatidylinositide-3 kinase (PI3K)/Akt signaling through HER3 to promote tumor growth and survival. The therapeutic benefit of HER2-targeting agents, which depend on PI3K/Akt inhibition, can be overcome by hyperactivation of the heregulin (HRG)/HER3 pathway. Here we describe an unbiased phenotypic combinatorial screening approach to identify a bispecific immunoglobulin G1 (IgG1) antibody against HER2 and HER3. In tumor models resistant to HER2-targeting agents, the bispecific IgG1 potently inhibits the HRG/HER3 pathway and downstream PI3K/Akt signaling via a "dock & block" mechanism. This bispecific IgG1 is a potentially effective therapy for breast cancer and other tumors with hyperactivated HRG/HER3 signaling.

PubMed: 29763625
DOI: 10.1016/j.ccell.2018.04.003

Experimental method

X-RAY DIFFRACTION (3.4 Å)