Related Experiment Video
Updated: Dec 12, 2025
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
A Fresh Approach to Targeting Aging Cells: CAR-T Cells Enhance Senolytic Specificity
1Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, CA 90095, USA; Medical Scientist Training Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Abstract:
Senescence is a critical factor in several diseases, yet senolytic therapies targeting senescent cells remain hindered by lack of specificity. In the June issue of Nature, Amor et al. (2020) develop chimeric antigen receptor (CAR)-T cells targeting uPAR, a novel senescent-cell marker, to treat liver adenocarcinoma and liver fibrosis.
Insights
Researchers developed chimeric antigen receptor (CAR)-T cells targeting urokinase plasminogen activator receptor (uPAR), a novel marker for senescent cells, to treat liver diseases. This approach aims to improve senolytic therapy specificity for conditions like liver adenocarcinoma and fibrosis.
Area of Science:
- Cellular senescence
- Immunotherapy
- Hepatology
Background:
- Cellular senescence plays a key role in various diseases.
- Current senolytic therapies lack specificity, limiting their effectiveness.
- Targeting senescent cells is a promising therapeutic strategy.
Purpose of the Study:
- To develop a novel senolytic therapy with enhanced specificity.
- To investigate the potential of targeting urokinase plasminogen activator receptor (uPAR) on senescent cells.
- To evaluate the efficacy of chimeric antigen receptor (CAR)-T cells against liver adenocarcinoma and liver fibrosis.
Main Methods:
- Development of CAR-T cells engineered to target uPAR.
- In vitro and in vivo models of liver adenocarcinoma and liver fibrosis.
- Assessment of CAR-T cell activity against senescent cells expressing uPAR.
Main Results:
- Successful development of uPAR-specific CAR-T cells.
- Demonstrated targeted elimination of senescent cells in preclinical models.
- Evidence of therapeutic potential in liver disease models.
Conclusions:
- uPAR is a viable target for senolytic therapy.
- CAR-T cell therapy targeting uPAR shows promise for treating senescent cell-associated liver diseases.
- This approach offers a potential solution to the specificity challenges in senolytic treatments.
Related Concept Videos
02:15Replicative Cell Senescence
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...