Table 1: Targeting leukocyte trafficking in inflammatory bowel disease.

TargetDrug typePreclinical efficacyTherapeuticClinical efficacy

Adhesion molecules
Integrins/ligandsAntisense MAdCAM-1 oligonucleotideTNBS colitis [49, 50]Natalizumab (humanized IgG4 mAb anti- 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- integrin mAB)CD (Phase II) [56]Reduced disease activity, good safety profile
Small molecule integrin antagonistDSS colitis [22]
Anti- and anti-MAdCAM-1 mAbT-cell transfer colitis [57] Vedolizumab/MLN-02 (humanized IgG4 mAb integrin)CD [58], UC Phase II [59, 60]Induced clinical response and remission, good safety profile
Anti-MAdCAM-1 mAbSAMP1/Yit mice [61]
Anti- mAbCotton top tamarin model [62]

ICAM-1/LFA-1Anti-ICAM-1 mAb Antisense ICAM-1 oligonucleotideDSS colitis [63, 64]Alicaforsen (ISIS2303) (antisense ICAM-1 oligonucleotide)UC (Phase II) [65, 66]Reduced disease activity, good safety profile
Anti-ICAM-1 mAbSAMP1/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/CXCL10Anti-CXCL10 mAbIL-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.