{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["20(12)"],"submitter":["Wang BT"],"funding":["IGM Biosciences Inc"],"pubmed_abstract":["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 xen"],"journal":["Molecular cancer therapeutics"],"pagination":["2483-2494"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9398157"],"repository":["biostudies-literature"],"pubmed_title":["Multimeric 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."],"pmcid":["PMC9398157"],"pubmed_authors":["Keyt BA","Hernandez G","Kothambawala T","Sinclair AM","Kotturi MF","Humke EW","Peterson MS","Saini AK","Wang BT","Matthew TJ","Calhoun SE","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"Multimeric 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.","description":"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 xen","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Dec","modification":"2026-07-14T16:34:10.531Z","creation":"2025-04-06T10:17:50.776Z"},"accession":"S-EPMC9398157","cross_references":{"pubmed":["34711645"],"doi":["10.1158/1535-7163.MCT-20-1132"]}}