Back to Search
Start Over
Oral Anti-Tumour Necrosis Factor Domain Antibody V565 Provides High Intestinal Concentrations, and Reduces Markers of Inflammation in Ulcerative Colitis Patients
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- V565 is an engineered TNFα-neutralising single domain antibody formulated into enteric coated mini-tablets to enable release in the intestine after oral administration as a possible oral treatment for inflammatory bowel disease (IBD). Following oral administration, ileal recovery of V565 was investigated in four patients with terminal ileostomy. Intestinal and systemic pharmacokinetics were measured in six patients with Crohn’s disease and evidence of target engagement assessed in five patients with ulcerative colitis. Following oral administration, V565 was detected at micromolar concentrations in ileal fluid from the ileostomy patients and in stools of the Crohn’s patients. In four of the five ulcerative colitis patients, biopsies taken after 7d dosing demonstrated V565 in the lamina propria with co-immunostaining on CD3+ T-lymphocytes and CD14+ macrophages. Phosphorylation of signalling proteins in biopsies taken after 7d oral dosing was decreased by approximately 50%. In conclusion, enteric coating of V565 mini-tablets provided protection in the stomach with gradual release in intestinal regions affected by IBD. Immunostaining revealed V565 tissue penetration and association with inflammatory cells, while decreased phosphoproteins after 7d oral dosing was consistent with V565-TNFα engagement and neutralising activity. Overall these results are encouraging for the clinical utility of V565 in the treatment of IBD.
- Subjects :
- 0301 basic medicine
Adult
Male
medicine.medical_specialty
medicine.medical_treatment
lcsh:Medicine
Inflammation
Gastroenterology
Antibodies
Article
03 medical and health sciences
Ileostomy
0302 clinical medicine
Oral administration
Internal medicine
medicine
Humans
Colitis
lcsh:Science
Aged
Lamina propria
Multidisciplinary
business.industry
Tumor Necrosis Factor-alpha
Stomach
lcsh:R
Middle Aged
medicine.disease
Ulcerative colitis
Enteric coating
Recombinant Proteins
Intestines
Crohn's disease
030104 developmental biology
medicine.anatomical_structure
030211 gastroenterology & hepatology
Colitis, Ulcerative
Female
lcsh:Q
Immunotherapy
medicine.symptom
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....43bbbf0b55ab1ec44357c69676ca8cfd