Methods: We evaluated whether human anti-VCAM-1 mAb binds to human or mouse VCAM-1. Leukocyte 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 cell counts in bronchoalveolar lavage (BAL) fluid, measured inflammatory cytokines, and examined histopathological features, including VCAM-1 immunohistochemistry.
Results: The human anti-VCAM-1 mAb bound to human and mouse VCAM-1 molecules and inhibited adhesion of human leukocytes in vitro. AHR and inflammatory cell counts in BAL fluid were reduced in mice treated with human anti-VCAM-1 mAb as compared to a control Ab. The levels of interleukin (IL)-5 and IL-13, and transforming growth factor-β in lung tissue were decreased in treated mice. Human anit-VCAM-1 mAb reduced goblet cell hyperplasia and peribronchial fibrosis. In vivo VCAM-1 expression decreased in treated group.
Conclusion: Human anti-VCAM-1 mAb can attenuate allergic inflammation and pathophysiological features of asthma in OVA induced murine asthma model. This data suggested that human anti-VCAM-1 mAb could be an additional anti-asthma therapeutic medicine.