Blocking Leukocyte Migration and Inflammation with Antibodies

Transendothelial migration (TEM) is the process by which leukocytes migrate out of the circulatory system and become irreversibly committed to entering the inflamed tissue. This process is promoted by interactions between adhesion molecules on the surface of the leukocytes and of the endothelial cells that line the blood vessels.

The inventors have discovered that two structurally related transmembrane proteins, namely CD99 and CD99L2, play a major, unexpected role in TEM. They showed that CD99 and CD99L2 are expressed on the surface of both leukocytes and endothelial cells where they mediate TEM of leukocytes through homophilic interactions.

The investigators generated monoclonal antibodies against human CD99 that blocked TEM by more than 90% in vitro. Antibodies against murine CD99 or CD99L2 reduce inflammation in a peritonitis inflammation model in vivo.

Potential Applications

Antibody therapy for chronic conditions such as arthritis, psoriasis and other inflammatory or auto-immune diseases.

Advantage

An antibody based therapy for inflammation that does not interfere with the immune response against infections