Glucocorticoid-induced TNFR-related protein (GITR, TNFRSF18), like DR5 and OX40, is a member of the TNF receptor superfamily. Similar to other members of the TNF receptor superfamily, strong GITR immunologic activity requires that three GITR proteins on the surface of a T cell be bound by a GITR ligand or an antibody. In the case of GITR, binding three or more GITR proteins with an IgM antibody sends a strong T cell immune stimulatory signal.
We anticipate that the multivalent binding provided by an IgM agonist antibody may produce a stronger immuno-oncology biological signal, as compared with a comparable IgG agonist antibody, particularly in the presence of immune-suppressive T regulatory cells.
GITR is considered to be a potentially important immuno-oncology target for both solid and liquid tumors. We hope to develop an anti-GITR IgM agonist antibody which is substantially more effective than IgG anti-GITR agonist antibodies at inducing an effective immune response for the treatment of solid and liquid tumors.