Table 1.
Targeting leukocyte trafficking in inflammatory bowel disease.
| Target | Drug type | Preclinical efficacy | Therapeutic | Clinical efficacy | |
|---|---|---|---|---|---|
| Adhesion molecules | |||||
| α 4 Integrins/ligands | Antisense MAdCAM-1 oligonucleotide | TNBS colitis [49, 50] | Natalizumab (humanized IgG4 mAb anti-α 4 integrin) | CD (Phase IV) [51, 52] | Prevented relapse, induced remission |
| Anti-VCAM-1 mAb | UC [53] | Pilot study | |||
| Anti-MAdCAM-1 mAb | DSS colitis [54, 55] | AJM300 (orally available anti-α 4 integrin mAB) | CD (Phase II) [56] | Reduced disease activity, good safety profile | |
| Small molecule α 4 integrin antagonist | DSS colitis [22] | ||||
| Anti-β 7 and anti-MAdCAM-1 mAb | T-cell transfer colitis [57] | Vedolizumab/MLN-02 (humanized IgG4 mAb α 4 β 7 integrin) | CD [58], UC Phase II [59, 60] | Induced clinical response and remission, good safety profile | |
| Anti-MAdCAM-1 mAb | SAMP1/Yit mice [61] | ||||
| Anti-α 4 β 7 mAb | Cotton top tamarin model [62] | ||||
|
| |||||
| ICAM-1/LFA-1 | Anti-ICAM-1 mAb Antisense ICAM-1 oligonucleotide | DSS colitis [63, 64] | Alicaforsen (ISIS2303) (antisense ICAM-1 oligonucleotide) | UC (Phase II) [65, 66] | Reduced disease activity, good safety profile |
| Anti-ICAM-1 mAb | SAMP1/Yit mice [67] | ||||
|
| |||||
| Chemokines | |||||
| CCR9/CCL25 | Anti-CCR9/CCL25 mAb Traficet-EN (CCX282-B) | SAMP1/Yit mice [68] TNF (DeltaARE) mice [69] | Traficet-EN/CCX282-B (small molecule CCR9 antagonist) | CD (Phase III) [70] | Induced clinical remission, good safety profile |
| CXCR3/CXCL10 | Anti-CXCL10 mAb | IL-10 KO [71, 72] DSS colitis [73] | MDX-1100 (humanized anti-CXCL10 mAb) | UC (Phase II) | NCT00295282 NCT00656890 |
CD: Crohn's disease; DSS: dextran sodium sulphate; ICAM-1: intercellular adhesion molecule 1; MadCAM: mucosal addressin-cell adhesion molecule 1; senescence accelerated mice (SAMP1/Yit); TNBS: trinitrobenzene sulfonic acid; UC: ulcerative colitis; V-CAM-1: vascular-cell adhesion molecule 1.