biostudies-literatureUnknown20(12)Wang BTIGM Biosciences IncDeath receptor 5 (DR5) is an attractive target for cancer therapy due to its broad upregulated expression in multiple cancers and ability to directly induce apoptosis. Though anti-DR5 IgG antibodies have been evaluated in clinical trials, limited efficacy has been attributed to insufficient receptor crosslinking. IGM-8444 is an engineered, multivalent agonistic IgM antibody with 10 binding sites to DR5 that induces cancer cell apoptosis through efficient DR5 multimerization. IGM-8444 bound to DR5 with high avidity and was substantially more potent than an IgG with the same binding domains. IGM-8444 induced cytotoxicity in a broad panel of solid and hematologic cancer cell lines but did not kill primary human hepatocytes <i>in vitro</i>, a potential toxicity of DR5 agonists. In multiple xenMolecular cancer therapeutics2483-2494https://www.ebi.ac.uk/biostudies/studies/S-EPMC9398157biostudies-literatureMultimeric Anti-DR5 IgM Agonist Antibody IGM-8444 Is a Potent Inducer of Cancer Cell Apoptosis and Synergizes with Chemotherapy and BCL-2 Inhibitor ABT-199.PMC9398157Keyt BAHernandez GKothambawala TSinclair AMKotturi MFHumke EWPeterson MSSaini AKWang BTMatthew TJCalhoun SEWang LfalseMultimeric Anti-DR5 IgM Agonist Antibody IGM-8444 Is a Potent Inducer of Cancer Cell Apoptosis and Synergizes with Chemotherapy and BCL-2 Inhibitor ABT-199.Death receptor 5 (DR5) is an attractive target for cancer therapy due to its broad upregulated expression in multiple cancers and ability to directly induce apoptosis. Though anti-DR5 IgG antibodies have been evaluated in clinical trials, limited efficacy has been attributed to insufficient receptor crosslinking. IGM-8444 is an engineered, multivalent agonistic IgM antibody with 10 binding sites to DR5 that induces cancer cell apoptosis through efficient DR5 multimerization. IGM-8444 bound to DR5 with high avidity and was substantially more potent than an IgG with the same binding domains. IGM-8444 induced cytotoxicity in a broad panel of solid and hematologic cancer cell lines but did not kill primary human hepatocytes <i>in vitro</i>, a potential toxicity of DR5 agonists. In multiple xen2021-01-01T00:00:00Z2021 Dec2026-07-14T16:34:10.531Z2025-04-06T10:17:50.776ZS-EPMC93981573471164510.1158/1535-7163.MCT-20-1132