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Published on: November 9, 2020
Synthetic Chimeric Antigen Lysosome-Associated Receptor Redirects Targeted Protein to Degradation
Yan Gao1, Haoxiang Li1, Tao Wang1
1State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, School of Biomedical Sciences, Hunan University, Changsha 410082, China.
Journal of the American Chemical Society
|June 25, 2026
Summary
Scientists developed synthetic chimeric antigen lysosome-associated receptors (CALARs) to target and degrade disease-causing proteins. This new method enhances immune response and reduces tumor size, offering a promising cell-based therapeutic platform.
Area of Science:
- Cell biology
- Immunology
- Biotechnology
Background:
- Cells use lysosomal degradation for protein clearance, a process with therapeutic potential.
- Existing lysosome-targeting chimeras (LYTACs) depend on endogenous receptors, limiting their effectiveness.
Purpose of the Study:
- To introduce synthetic chimeric antigen lysosome-associated receptors (CALARs) for enhanced protein degradation.
- To develop a cell-based therapeutic platform independent of native receptor trafficking.
Main Methods:
- Engineered CALARs encoded within circular RNA.
- Reprogrammed cells to sort extracellular proteins to lysosomes.
- Assessed sustained suppression of immune checkpoints and growth factor receptors.
Main Results:
- CALARs enabled sustained protein suppression for over one week.
- Demonstrated enhanced immune activation.
- Significantly reduced tumor burden in vivo.
Conclusions:
- CALARs offer a novel, modular, and genetically encodable platform for protein modulation.
- This technology advances cell-based therapeutics by overcoming limitations of current LYTACs.
- CALARs show potential for cancer therapy by enhancing immune response and reducing tumors.
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