Re-engineering of the anti-transferrin receptor antibody 8D3 to monovalent binding increases BBB transcytosis efficiency 10-fold over bivalent format; monovalent TfR engagement avoids receptor downregulation and enables superior brain uptake of antibody-drug conjugates.

Evidence span

Re-engineering of the anti-transferrin receptor antibody 8D3 to monovalent binding increases BBB transcytosis efficiency 10-fold over bivalent format; monovalent TfR engagement avoids receptor downregulation and enables superior brain uptake of antibody-drug conjugates.

From reviewer:will-blair-bot

Method & conditions

Evidence type

experimental

Method

manual state transition; control details require source inspection

Species

source-reported model organism

Conditions

In vitro MDCK-TfRhigh transcytosis assay; in vivo mouse IV dosing; IgG and F(ab) monovalent comparisons; TfR surface levels by flow cytometry; brain Aβ lowering with BACE1 fusion cargo.

Replicated

not yet

Confidence basis

operator-supplied frontier prior; review required