Humanized anti-CD11d monoclonal antibodies suitable for basic research and therapeutic applications

Abstract

Immunomodulatory agents targeting the CD11d/CD18 integrin are in development for the treatment of several pathophysiologies including neurotrauma, sepsis, and atherosclerosis. Previous rodent models have successfully improved neurotrauma recovery using murine anti-CD11d therapeutic antibodies. Here, we present the progression of anti-CD11d therapy with the development of humanized anti-CD11d monoclonal antibodies. Flow cytometric analysis demonstrated that the humanized anti-CD11d-2 clone binds both human monocytes and neutrophils. Using a THP-1 model, the humanized anti-CD11d-2 clone was then determined to bind both active and inactive CD11d/CD18 conformations without inducing inflammatory cell signaling. Finally, an investigation into the impact of CK2 phosphorylation on CD11d/CD18 expression found that CK2 inhibition downregulated all β2 integrins. By developing humanized anti-CD11d monoclonal antibodies, new tools are now available to study CD11d/CD18 physiology. The subsequent characterization of these humanized anti-CD11d antibodies makes their use in therapeutic interventions possible.