A novel human anti‐VCAM‐1 monoclonal antibody ameliorates airway inflammation and remodelling

Abstract

Asthma is a chronic inflammatory disease induced by Type 2 helper T cells and eosinophils. Vascular cell adhesion molecule-1 (VCAM-1) has been implicated in recruiting eosinophils and lymphocytes to pathological sites in asthma as a regulatory receptor. Accordingly, monoclonal antibody (mAb) against VCAM-1 may attenuate allergic inflammation and pathophysiological features of asthma. We attempted to evaluate whether a recently developed human anti-VCAM-1 mAb can inhibit the pathophysiological features of asthma in a murine asthma model induced by ovalbumin (OVA). Leucocyte adhesion inhibition assay was performed to evaluate the in vitro blocking activity of human anti-VCAM-1 mAb. OVA-sensitized BALB/c mice were treated with human anti-VCAM-1 mAb or isotype control Ab before intranasal OVA challenge. We evaluated airway hyperresponsiveness (AHR) and bronchoalveolar lavage fluid analysis, measured inflammatory cytokines and examined histopathological features. The human anti-VCAM-1 mAb bound to human and mouse VCAM-1 molecules and inhibited adhesion of human leucocytes in vitro. AHR and inflammatory cell counts in bronchoalveolar lavage fluid were reduced in mice treated with human anti-VCAM-1 mAb as compared with a control Ab. The levels of interleukin (IL)-5 and IL-13, as well as transforming growth factor-β, in lung tissue were decreased in treated mice. Human anti-VCAM-1 mAb reduced goblet cell hyperplasia and peribronchial fibrosis. In vivo VCAM-1 expression decreased in the treated group. In conclusion, human anti-VCAM-1 mAb attenuated allergic inflammation and the pathophysiological features of asthma in OVA-induced murine asthma model. The results suggested that human anti-VCAM-1 mAb could potentially be used as an additional anti-asthma therapeutic medicine.

Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer

“…In the same model, the administration of an anti-VCAM-1 antibody (429) also had reduced the recruitment of mast cell precursors to the inflamed lung [ 39 ]. Furthermore, the anti-VCAM-1 antibody attenuated macrophage, neutrophil, and eosinophil recruitment in an OVA-induced murine allergic asthma model [ 40 ].…”

“…They showed that all three antibodies significantly inhibited the recruitment of eosinophils and lymphocytes into BAL fluid and decreased inflammation in lung tissue, suggesting that α4 integrin and VCAM-1 may have important roles in the recruitment of T cells and eosinophils in OVA-induced airway inflammation [ 77 ]. Recently, Lee et al developed a novel human anti-VCAM-1 monoclonal antibody (HD101) that binds strongly to Ig-like domains 1 and 2 of human and mouse VCAM-1 [ 40 ]. They confirmed that the antibody can effectively ameliorate eosinophilic inflammation and airway hyperresponsiveness in the OVA mouse model [ 40 ].…”

“…Recently, Lee et al developed a novel human anti-VCAM-1 monoclonal antibody (HD101) that binds strongly to Ig-like domains 1 and 2 of human and mouse VCAM-1 [ 40 ]. They confirmed that the antibody can effectively ameliorate eosinophilic inflammation and airway hyperresponsiveness in the OVA mouse model [ 40 ]. Further, they also showed that the antibody inhibits the adhesion of U937, EoL-1, and CD4 + T cells to human VCAM-1 [ 40 ].…”

Zingiber mioga (Thunb.) Roscoe attenuates allergic asthma induced by ovalbumin challenge

“…The development of allergic asthma is associated with overexpression of iNOS in the airways, which results in an asthmatic response. Previous studies have demonstrated that iNOS expression is associated with the induced activation of T-helper (Th)2 lymphocytes, which results in the pathophysiological alterations that occur in asthma (2,3). Th2 lymphocytes produce various Th2 cytokines that have important roles in the development of allergic asthma (3).…”

“…Previous studies have demonstrated that iNOS expression is associated with the induced activation of T-helper (Th)2 lymphocytes, which results in the pathophysiological alterations that occur in asthma (2,3). Th2 lymphocytes produce various Th2 cytokines that have important roles in the development of allergic asthma (3). Th2 cytokines include interleukin (IL)-4, IL-5 and IL-13, and induce secretion of allergen-specific immunoglobulin (Ig) E, chemokines and eosinophils, as well as mucus production.…”