"Endothelial Antibody Factory" at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases.

Autor: Thinard R; ALSaTECH, Inc., 300 Market Street, Boston, MA 02135, USA., Farkas AE; Institute of Biophysics, Biological Research Centre, Eötvös Lorand Research Network (ELKH), 6726 Szeged, Hungary., Halasa M; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, 04-141 Warsaw, Poland.; Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-079 Lublin, Poland., Chevalier M; ALSaTECH, Inc., 300 Market Street, Boston, MA 02135, USA., Brodaczewska K; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, 04-141 Warsaw, Poland., Majewska A; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, 04-141 Warsaw, Poland.; Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland., Zdanowski R; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, 04-141 Warsaw, Poland., Paprocka M; Hirszfeld Institute of Immunol & Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland., Rossowska J; Hirszfeld Institute of Immunol & Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland., Duc LT; Institute of Biophysics, Biological Research Centre, Eötvös Lorand Research Network (ELKH), 6726 Szeged, Hungary.; Doctoral School of Biology, University of Szeged, 6726 Szeged, Hungary., Greferath R; ALSaTECH, Inc., 300 Market Street, Boston, MA 02135, USA., Krizbai I; Institute of Biophysics, Biological Research Centre, Eötvös Lorand Research Network (ELKH), 6726 Szeged, Hungary.; Institute of Life Sciences, Vasile Goldiş Western University of Arad, 310025 Arad, Romania., Van Leuven F; LEGTEGG, Katholieke Universiteit Leuven, 3000 Leuven, Belgium., Kieda C; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, 04-141 Warsaw, Poland.; Centre for Molecular Biophysics, UPR 4301 CNRS, 45071 Orleans, France., Nicolau C; ALSaTECH, Inc., 300 Market Street, Boston, MA 02135, USA.; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2022 Jul 06; Vol. 14 (7). Date of Electronic Publication: 2022 Jul 06.
DOI: 10.3390/pharmaceutics14071418
Abstrakt: The failures of anti-β-amyloid immunotherapies suggested that the very low fraction of injected antibodies reaching the brain parenchyma due to the filtering effect of the BBB may be a reason for the lack of therapeutic effect. However, there is no treatment, as yet, for the amyotrophic lateral sclerosis (ALS) despite substantial evidence existing of the involvement of TDP-43 protein in the evolution of ALS. To circumvent this filtering effect, we have developed a novel approach to facilitate the penetration of antibody fragments (Fabs) into the brain parenchyma. Leveraging the homing properties of endothelial progenitor cells (EPCs), we transfected, ex vivo, such cells with vectors encoding anti-β-amyloid and anti-TDP43 Fabs turning them into an "antibody fragment factory". When injected these cells integrate into the BBB, where they secrete anti-TDP43 Fabs. The results showed the formation of tight junctions between the injected engineered EPCs and the unlabeled resident endothelial cells. When the EPCs were further modified to express the anti-TDP43 Fab, we could observe integration of these cells into the vasculature and the secretion of Fabs. Results confirm that production and secretion of Fabs at the BBB level leads to their migration to the brain parenchyma where they might exert a therapeutic effect.
Databáze: MEDLINE
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