Cytolin® is a mouse monoclonal antibody that was originally developed to identify a specific type of immune cell called a cytotoxic T cell, or CTL. Subsequent work showed that the antigen Cytolin® bound to was the cellular antigen CD11a, which along with CD18 makes up the cellular adhesion molecule LFA-1. In the 1990s a number of researchers reported that LFA-1 appeared to be critical for HIV infection. These observations, along with the unique reactivity of Cytolin® for CTLs, prompted the company to explore the administration of Cytolin® to HIV-infected people to determine if it could perturb the natural course of HIV infection. These uncontrolled clinical studies showed treatment with Cytolin® appeared to stabilize immunity and in some cases reduce viral burden.
Based on these encouraging findings the company decided to explore exactly where Cytolin® bound to CD11a. LFA-1 normally functions in the body as an adhesion molecule and is a critical component of the immune response. Under normal circumstances LFA-1 on immune cells binds to its cognate receptor (called ICAM) on the other cells and allows for a tight connection between cells so that a productive immune response can occur. Interestingly, virtually all other anti-CD11as antibodies available at that time were targeted to the site of the CD11a molecule that bound to ICAM, resulting in antibodies that block immune activity. The results of the binding studies with Cytolin® showed that unlike other CD11a specific antibodies, Cytolin® did not bind to the ICAM binding region of the molecule. As a consequence of this unique specificity, Cytolin® did not block the normal function of CD11a.
Further work showed that in addition to cytotoxic T lymphocytes (CTLs) Cytolin® also appears to bind another type of immune cell called a dendritic cells (DCs) . Both of these cells are critical to the control of viral burden in HIV infected individuals. By binding to these cells, Cytolin® appears induce an antiviral activity that can impede infection of new cells and presumably lead to a reduction in viral burden. A fully humanized version of Cytolin® will begin testing this year to confirm and extend our understanding of how to apply this new approach to the treatment of HIV/AIDS.
