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CBL-B - An upcoming immune-oncology target
Riccardo Fusco1, Zeinab Saedi1, Imma Capriello1
1Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, and Czech Advanced Technology and Research Institute, Palacky University, Olomouc, Czechia.
Introduction:
The E3 ubiquitin ligase Cbl-b is a novel target in immune-oncology, with critical roles in regulating T-cell activation and signaling pathways. By facilitating the ubiquitination and degradation of key signaling proteins, Cbl-b modulates immune responses, maintaining immune homeostasis and preventing unwarranted T-cell proliferation. The therapeutic potential of Cbl-b as a cancer immunotherapy target is underscored by its contribution to an immunosuppressive tumor microenvironment, with efforts currently underway to develop small-molecule inhibitors.
Areas Covered:
We reviewed the small molecules, and antibody-drug conjugates targeting Cbl-b from 2018 to 2024. The patents were gathered through publicly available databases and analyzed with in-house developed cheminformatic workflow, described within the manuscript.
Expert Opinion:
Targeting Cbl-b presents a promising approach in immuno-oncology, offering a novel pathway to potentiate the immune system's ability to combat cancer beyond PDL1/PD1 inhibition. The development and clinical advancement of Cbl-b inhibitors, as evidenced by the ongoing trials, mark a significant step toward harnessing this target for therapeutic benefits. Overall, the strategic inhibition of Cbl-b holds substantial promise for improving cancer immunotherapy outcomes, heralding a new era in the fight against cancer.
Insights
The E3 ubiquitin ligase Cbl-b, a novel immune-oncology target, regulates T-cell activation. Inhibiting Cbl-b shows promise for enhancing cancer immunotherapy and overcoming tumor-induced immunosuppression.
Area of Science:
- Immuno-oncology
- Cancer immunotherapy
- Ubiquitin ligase signaling
Background:
- Cbl-b (E3 ubiquitin ligase) is crucial for T-cell activation and immune homeostasis.
- Cbl-b activity contributes to an immunosuppressive tumor microenvironment.
- Cbl-b regulates key signaling proteins via ubiquitination and degradation.
Purpose of the Study:
- To review small molecules and antibody-drug conjugates targeting Cbl-b from 2018-2024.
- To analyze the therapeutic potential of Cbl-b inhibition in cancer immunotherapy.
- To explore Cbl-b as a target beyond PDL1/PD1 inhibition.
Main Methods:
- Patent literature review from 2018 to 2024.
- Utilized publicly available patent databases.
- Applied an in-house developed cheminformatic workflow for analysis.
Main Results:
- Identified and reviewed small molecules and antibody-drug conjugates targeting Cbl-b.
- Analysis of patents highlights ongoing development in Cbl-b inhibitor research.
- Evidence of clinical advancement and ongoing trials for Cbl-b inhibitors.
Conclusions:
- Targeting Cbl-b offers a novel strategy in immuno-oncology.
- Cbl-b inhibition shows potential to enhance cancer immunotherapy outcomes.
- Strategic inhibition of Cbl-b represents a significant advancement in cancer treatment.
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