Anti-VEGFR2 F(ab')<sub>2</sub> drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38092739.
- Also identified by DOI 10.1038/s41467-023-43847-2 and PMC identifier 10719340.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Poor renal distribution of antibody-based drugs is the key factor contributing to low treatment efficiency for renal diseases and side effects. Here, we prepare F(ab')<sub>2</sub> fragmented vascular endothelial growth factor receptor 2 antibody (anti-VEGFR2 (F(ab')<sub>2</sub>) to block VEGFR2 overactivation in diabetic nephropathy (DN). We find that the anti-VEGFR2 F(ab')<sub>2</sub> has a higher accumulation in DN male mice kidneys than the intact VEGFR2 antibody, and simultaneously preserves the binding ability to VEGFR2. Furthermore, we develop an antibody fragment drug conjugate, anti-VEGFR2 F(ab')<sub>2</sub>-SS31, comprising the anti-VEGFR2 F(ab')<sub>2</sub> fragment linked to the mitochondria-targeted antioxidant peptide SS31. We find that introduction of SS31 potentiates the efficacy of anti-VEGFR2 F(ab')<sub>2</sub>. These findings provide proof of concept for the premise that antibody fragment drug conjugate improves renal distribution and merits drug validation in renal disease therapy.
Medical subject headings
- Diabetic Nephropathies
- Immunoconjugates
- Diabetes Mellitus