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.
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
Bridged Bicyclo Compounds, Heterocyclic
/ pharmacology
Cell Line, Tumor
Disease Models, Animal
Female
Genes, bcl-2
/ genetics
Humans
Immunoglobulin M
/ pharmacology
Mice
Mice, Nude
Receptors, TNF-Related Apoptosis-Inducing Ligand
/ antagonists & inhibitors
Sulfonamides
/ pharmacology
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
31
12
2020
revised:
07
07
2021
accepted:
15
09
2021
pubmed:
30
10
2021
medline:
26
3
2022
entrez:
29
10
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 34711645
pii: 1535-7163.MCT-20-1132
doi: 10.1158/1535-7163.MCT-20-1132
pmc: PMC9398157
doi:
Substances chimiques
Antineoplastic Agents
0
Bridged Bicyclo Compounds, Heterocyclic
0
Immunoglobulin M
0
Receptors, TNF-Related Apoptosis-Inducing Ligand
0
Sulfonamides
0
venetoclax
N54AIC43PW
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2483-2494Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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