IGM-8444:  Death Receptor 5 Agonist IgM Antibody

IGM-8444 is an IgM antibody targeting Death Receptor 5 (DR5) for the treatment of patients with solid and hematologic malignancies. DR5 is a member of the tumor necrosis factor receptor superfamily (TNFrSF) and is often expressed on the surface of cancer cells.

Similar to other members of the TNFrSF, strong signaling to effect a biological response requires that three or more DR5 receptor proteins be cross-linked together on the surface of a cancer cell through the binding of either the natural DR5 ligand (TRAIL) or an antibody or other therapeutic drug that can efficiently cross-link the DR5 receptors. Binding and cross-linking of DR5 receptors sends a signal to the cancer cell to induce programmed death of the cancer cell, also known as apoptosis.

DR5 Signaling to Induce Programmed Death of Cancer Cells


DR5 IgM antibodies have the capacity for multivalent binding of DR5, which results in three or more cross-linked DR5 receptors on the cell surface and efficiently sends an apoptotic signal to the cancer cell. In our laboratory studies, DR5 IgM antibodies showed significantly enhanced in vitro potency in killing cancer cells compared to IgG antibodies with the same binding units.