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Death Receptor 5 (DR5)

Death Receptor 5 (DR5, TNRSF10B, TRAILR2) is a member of the TNF receptor superfamily which is displayed on the surface of tumor cells. Similar to other members of the TNF receptor superfamily, strong DR5 immunologic activity requires that three DR5 proteins on the surface of a tumor cell be bound together by a DR5 ligand or an antibody in order to send a strong biological signal. In the case of DR5, binding three or more DR5 proteins with an IgM antibody sends a strong apoptotic signal (commit suicide or programmed cell death) to the tumor cell.

DR5 is present on a broad range of solid tumors (colon, breast, prostate and pancreatic), as well as lymphomas and leukemias. A number of IgG anti-DR5 antibodies were taken into clinical trials by pharmaceutical and biotech companies and failed to show adequate efficacy. We believe that IgG anti-DR5 antibodies, which can only bind two DR5 targets, may not have been able to produce a strong enough apoptotic signal.

The multivalent binding provided by an IgM anti-DR5 agonist antibody may produce a much stronger apoptotic signal, as compared with an IgG anti-DR5 antibody. IGM Biosciences has shown that IgM anti-DR5 antibodies are much more effective in vitro and in animal models as contrasted with comparable IgG anti-DR5 antibodies.

IgM anti-DR5 antibodies have been shown to be substantially more potent in vitro as compared with comparable IgG antibodies

 

We hope that our anti-DR5 IgM agonist antibody will be able to safely and effectively treat solid and blood cell tumors as a single agent and in combination with chemotherapeutic drugs, immune checkpoint antibodies and other therapeutic antibodies.