Targeted topical anti-α4β7 integrin antibody results in reduced accumulation of α4β7 memory T-cells in gut tissue in DSS-induced colitis mice
The results from this preclinical study point to the potential for increased efficacy with high concentrations in local inflamed tissues.
Systemically administered anti-α4β7 integrin antibodies such as Vedolizumab have been approved for the treatment of Crohn’s disease and ulcerative colitis. The objective of this preclinical study was to assess whether intracecally (IC) delivered anti-mouse α4β7 integrin antibody (DATK32) might penetrate disrupted mucosa and confer efficacy when compared with systemic intraperitoneal (IP) injection in DSS-induced colitis mice.
What did we find?
Targeted IC delivery led to significantly higher drug exposure in colon contents and tissues with limited blood exposure
when compared with IP delivery in an acute colitis model.1
Although the mechanism of action is unclear, this study suggests topically delivered anti-α4β7 integrin antibody may be an efficacious treatment in IBD.1
“Direct administration of drug therapies via ingestible technologies shows tremendous promise to improve treatment outcomes in patients with gastrointestinal diseases. Administering a high therapeutic dose directly to the site of disease with a noninvasive method of delivery could be key to increasing treatment efficacy for these burdensome disorders.”
William Sandborn, MD, chief of gastroenterology and director of the Inflammatory Bowel Disease Center at UC San Diego Health
- Lee NS, Singh S, Luo A, et al. Targeted topical anti-α4β7 integrin antibody results in reduced accumulation of α4β7 memory T-cells in gut tissue in DSS-induced colitis mice. Poster presented at: American College of Gastroenterology Annual Scientific Meeting, October 25-30, 2019, San Antonio, Texas.