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- W4313237453 abstract "Abstract Twenty-five years ago, we reported that agonist anti-CD137 monoclonal antibodies eradicated transplanted mouse tumors because of enhanced CD8+ T-cell antitumor immunity. Mouse models indicated that anti-CD137 agonist antibodies synergized with various other therapies. In the clinic, the agonist antibody urelumab showed evidence for single-agent activity against melanoma and non-Hodgkin lymphoma but caused severe liver inflammation in a fraction of the patients. CD137's signaling domain is included in approved chimeric antigen receptors conferring persistence and efficacy. A new wave of CD137 agonists targeting tumors, mainly based on bispecific constructs, are in early-phase trials and are showing promising safety and clinical activity. Significance: CD137 (4-1BB) is a costimulatory receptor of T and natural killer lymphocytes whose activity can be exploited in cancer immunotherapy strategies as discovered 25 years ago. Following initial attempts that met unacceptable toxicity, new waves of constructs acting agonistically on CD137 are being developed in patients, offering signs of clinical and pharmacodynamic activity with tolerable safety profiles." @default.
- W4313237453 created "2023-01-06" @default.
- W4313237453 creator A5025411417 @default.
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- W4313237453 creator A5035295243 @default.
- W4313237453 creator A5044206952 @default.
- W4313237453 creator A5063974312 @default.
- W4313237453 date "2022-12-28" @default.
- W4313237453 modified "2023-10-15" @default.
- W4313237453 title "CD137 (4-1BB)-Based Cancer Immunotherapy on Its 25th Anniversary" @default.
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