Targeting inflammation with collagen-binding antibodies

Autor: Eiji Yuba, Jeffrey A. Hubbell, Michal M. Raczy, Ako Ishihara, Jun Ishihara, Kiyomitsu Katsumata, Aslan Mansurov
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Decorin
Pulmonary Fibrosis
Anti-Inflammatory Agents
Arthritis
02 engineering and technology
Biochemistry
Extracellular matrix
0302 clinical medicine
Transforming Growth Factor beta
Pandemic
Pulmonary fibrosis
Molecular Targeted Therapy
Lung
Research Articles
Mice
Inbred BALB C
0303 health sciences
Multidisciplinary
biology
SciAdv r-articles
Antigen binding
021001 nanoscience & nanotechnology
medicine.anatomical_structure
Collagen
medicine.symptom
Antibody
0210 nano-technology
Research Article
2019-20 coronavirus outbreak
Coronavirus disease 2019 (COVID-19)
medicine.drug_class
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Sialoglycoproteins
Inflammation
Antibodies
Anti-inflammatory
03 medical and health sciences
Rheumatology
medicine
Animals
Humans
030304 developmental biology
030203 arthritis & rheumatology
Tumor Necrosis Factor-alpha
business.industry
medicine.disease
Peptide Fragments
Mice
Inbred C57BL
030104 developmental biology
Immunology
biology.protein
Cancer research
business
Zdroj: Nature Reviews Rheumatology
Science Advances
ISSN: 1759-4804
1759-4790
DOI: 10.1038/s41584-019-0350-3
Popis: Inflammation targeting through collagen affinity improves antibody therapeutic ability.
Enhancing the therapeutic efficacy of drugs for inflammatory diseases is of high demand. One possible approach is targeting drugs to the extracellular matrix of the inflamed area. Here, we target collagens in the matrix, which are inaccessible in most tissues yet are exposed to the bloodstream in the inflamed area because of vascular hyperpermeability. We conferred collagen affinity to anti–tumor necrosis factor-α (α-TNF) antibody by conjugating a collagen-binding peptide (CBP) derived from the sequence of decorin. CBP–α-TNF accumulated in the inflamed paw of the arthritis model, and arthritis development was significantly suppressed by treatment with CBP–α-TNF compared with the unmodified antibody. Similarly, CBP–anti-transforming growth factor-β (α–TGF-β) accumulated in the inflamed lung of pulmonary fibrosis model and significantly suppressed pulmonary fibrosis compared with the unmodified antibody. Together, collagen affinity enables the anticytokine antibodies to target arthritis and pulmonary fibrosis accompanied by inflammation, demonstrating a clinically translational approach to treat inflammatory diseases.
Databáze: OpenAIRE
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