Development of Drugs Targeting Leukocyte Trafficking for IBD

Inflammatory bowel disease (IBD) is characterized by immunological-inflammatory features involving intestinal accumulation of immune cells, myeloid cells and lymphocytes. One of the major biological pathways mediating the development of inflammation in the intestine during IBD is the highly complex interplay of interactions between circulating leukocytes and intestinal vascular endothelial cells leading to the migration of the leukocyte across the endothelium and into the intestinal mucosa. Therefore, sterilisation of the inflammatory substrate resulting from the blockade of leukocyte migration to the intestine is one of the main strategies used to control disease and symptom alleviation, and thus a promising platform for drug development.

Fig. 1.Overview of lymphocyte trafficking including current and emerging drug therapies targeting these mechanisms in IBD. (Wyatt, et al., 2021)

Our Services

The team at Ace Therapeutics consists of leading experts in the field of antibody engineering and drug discovery, with many years of experience in IBD drug development, immunology and cell biology, designing and implementing preclinical studies. We are focused on the mechanism of leukocyte function and migration in IBD and applying new therapies in this field.

Based on a sound theoretical background and substantial practical experience, we help our clients design leukocyte trafficking therapies to increase their efficacy and reduce their side effects, to be able to better assess the mechanism of action of leukocyte adhesion during mucosal homing with interaction of the leukocyte with other intestinal mucosal cells.

Development Services for Drugs Targeting Leukocyte Trafficking

We help pharmaceutical and biotech companies develop drugs that target integrins, chemokines or receptors involved in leukocyte intestinal trafficking.

• Targeting CD18 integrin/ICAM-1 pathway in IBD
• Targeting α4 integrins (CD49d) and their ligands: α4β1/VCAM-1 and α4β7/MAdCAM-1
• Targeting of α4 integrins/ligands in IBD
• Targeting αEβ7 integrin (CD103)
• Targeting of β7 integrins in IBD
• Targeting intestinal-specific chemokine/chemokine receptor complexes
• Targeting Sphingosine-1-phosphate (S1P) receptors in IBD

Evaluation of the Safety and Efficacy of Drugs Targeting Leukocyte Trafficking

We provides colitis animal models (e.g., the adoptive T cell transfer model of chronic colitis) to evaluate the safety and efficacy of drugs targeting leukocyte trafficking, providing important data to support IBD drug development.

• By flow cytometry, the integral leukocyte phenotype and its functional activity in blood or intestinal tissue are examined to investigate the underlying mechanisms of drug influences in zymosan-induced peritonitis.
• Measuring serum levels of inflammatory factors (e.g., IL-6, TNF-α, IL-1β) to evaluate the antiphlogistic properties of drugs acting on leukocyte trafficking.
• Study the expression of certain proteins (e.g.,, adhesion molecules, chemokines) to see how targeted drugs are changing leukocyte migration in various stages (e.g., recruitment, adhesion).

Ace Therapeutics offers focused preclinical studies validating the targeting of specific steps of the leukocyte adhesion cascade for therapeutic approaches of IBD. Experiments includes a simplified model of leukocyte migration cascade, target screen and validation, and mechanistic studies of leukocyte migration. Please do not hesitate to contact us. We would be glad to hear from you.