A Site-Specific MiniAp4–Trastuzumab Conjugate Prevents Brain Metastasis DOI Creative Commons
Mariam Masmudi‐Martín, Benjamí Oller‐Salvia, M. Perea

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: 22(3), P. 1384 - 1395

Published: Feb. 10, 2025

Monoclonal antibodies (mAbs) are changing cancer treatments. However, the presence of blood–brain barrier (BBB) and blood–tumor (BTB) limits use mAbs to treat brain or metastasis. Molecules that hijack endogenous transport mechanisms on endothelium (brain shuttles) have been shown increase large molecules nanoparticles across BBB. Among these shuttles, protease-resistant peptides such as MiniAp-4 particularly efficient. Here, we report synthesis, characterization, evaluation site-specific mAb–brainshuttle antibody conjugates (ASC) based anti-HER2 mAb trastuzumab (Tz) four MiniAp-4. The ASCs preserve binding cell cycle arrest capacity Tz. ASC displays enhanced an in vitro BBB cellular model with respect Tz conjugated Angiopep-2, shuttle has advanced most clinical trials. More importantly, Tz-MiniAp4 a murine metastasis demonstrated peptide showed preferential BBB/BTB, displaying marked therapeutic effect protecting against development. technology described herein could be applied any interest central nervous system-related diseases. enhances monoclonal trastuzumab, preventing

Language: Английский

A Site-Specific MiniAp4–Trastuzumab Conjugate Prevents Brain Metastasis DOI Creative Commons
Mariam Masmudi‐Martín, Benjamí Oller‐Salvia, M. Perea

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: 22(3), P. 1384 - 1395

Published: Feb. 10, 2025

Monoclonal antibodies (mAbs) are changing cancer treatments. However, the presence of blood–brain barrier (BBB) and blood–tumor (BTB) limits use mAbs to treat brain or metastasis. Molecules that hijack endogenous transport mechanisms on endothelium (brain shuttles) have been shown increase large molecules nanoparticles across BBB. Among these shuttles, protease-resistant peptides such as MiniAp-4 particularly efficient. Here, we report synthesis, characterization, evaluation site-specific mAb–brainshuttle antibody conjugates (ASC) based anti-HER2 mAb trastuzumab (Tz) four MiniAp-4. The ASCs preserve binding cell cycle arrest capacity Tz. ASC displays enhanced an in vitro BBB cellular model with respect Tz conjugated Angiopep-2, shuttle has advanced most clinical trials. More importantly, Tz-MiniAp4 a murine metastasis demonstrated peptide showed preferential BBB/BTB, displaying marked therapeutic effect protecting against development. technology described herein could be applied any interest central nervous system-related diseases. enhances monoclonal trastuzumab, preventing

Language: Английский

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