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PD-L1 Crosslinking as a New Strategy of 4-1BB Agonism Immunotherapy
Fei Shu1, Salman R Punekar2, Vamsidhar Velcheti2
1Department of Pathology, New York University Grossman School of Medicine, NYU Langone Health, New York, New York.
Abstract:
4-1BB has been considered a promising target in cancer immunotherapy for decades. Nevertheless, early 4-1BB-targeted agents demonstrated significant liver immuno-toxicity. A new wave of 4-1BB-based therapy is being developed to circumvent hepatotoxicity with a bispecific molecule that directs 4-1BB agonism to the tumor microenvironment by targeting tumor-associated immune checkpoint molecule PD-L1. See related article by Peper-Gabriel et al., p. 3387.
Insights
New bispecific antibodies target 4-1BB agonism to tumors, reducing liver toxicity common in early cancer immunotherapy. This approach aims to improve safety for 4-1BB-based treatments.
Area of Science:
- Immunology
- Oncology
- Drug Development
Background:
- 4-1BB is a validated target for cancer immunotherapy.
- Early 4-1BB agonists caused significant liver toxicity, limiting their clinical use.
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