Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/223094
A site-specific MiniAp4-Trastuzumab conjugate prevents brain metastasis
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Monoclonal antibodies (mAbs) are changing cancer treatments. However, the presence of the blood–brain barrier (BBB) and the blood–tumor barrier (BTB) limits the use of mAbs to treat brain cancer or brain metastasis. Molecules that hijack endogenous transport mechanisms on the brain endothelium (brain shuttles) have been shown to increase the transport of large molecules and nanoparticles across the BBB. Among these shuttles, protease-resistant peptides such as MiniAp-4 are particularly efficient. Here, we report the synthesis, characterization, and evaluation of site-specific mAb–brainshuttle antibody conjugates (ASC) based on the anti-HER2 mAb trastuzumab (Tz) and four molecules of MiniAp-4. The ASCs preserve the binding and cell cycle arrest capacity of Tz. MiniAp-4 ASC displays enhanced transport across an in vitro BBB cellular model with respect to Tz and Tz conjugated to Angiopep-2, the brain shuttle that has advanced the most in clinical trials. More importantly, evaluation of Tz-MiniAp4 in a murine brain metastasis model demonstrated that the protease-resistant peptide showed preferential transport across the BBB/BTB, displaying a marked therapeutic effect and protecting against metastasis development. The technology described herein could be applied to any antibody of interest to treat central nervous system-related diseases. MiniAp-4 enhances the brain transport of the monoclonal antibody trastuzumab, preventing brain metastasis.
Matèries
Matèries (anglès)
Citació
Citació
MASMUDI-MARTÍN, Mariam, OLLER SALVIA, Benjamí, PEREA, María, TEIXIDÓ TURÀ, Meritxell, VALIENTE, Manuel, GIRALT LLEDÓ, Ernest, SÁNCHEZ-NAVARRO, Macarena. A site-specific MiniAp4-Trastuzumab conjugate prevents brain metastasis. _Molecular Pharmaceutics_. 2025. Vol. 22, núm. 3, pàgs. 1384-1395. [consulta: 2 de gener de 2026]. ISSN: 1543-8384. [Disponible a: https://hdl.handle.net/2445/223094]