Related Experiment Video
Updated: Jan 10, 2026
Protein Engineering by Yeast Surface Display
Published on: November 29, 2024
A yeast surface display platform for characterizing CAR T cell responses to cancer antigens
Marcus Deichmann1, Giovanni Schiesaro1, Keerthana Ramanathan2
1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
Abstract:
Chimeric antigen receptor (CAR) T cells have become an established immunotherapy with promising results for the treatment of hematological malignancies. However, modulation of the targeted antigen's surface level in cancer cells affects the quality and safety of CAR-T cell therapy. Here we present an engineered yeast-based antigen system for simulation of cancer cells with precise regulation of surface-antigen densities, providing a tool for controlled activation of CAR T cells and systematic assessment of antigen density effects. This Synthetic Cellular Advanced Signal Adapter (SCASA) system uses G protein-coupled receptor signaling to control cancer antigen densities on the yeast surface and provides a customizable platform allowing selectable signal inputs and modular pathway engineering for precise output fine-tuning. In relation to CD19+ cancers, we demonstrate synthetic cellular communication between CD19-displaying yeast and human CAR T cells as well as applications in high-throughput characterization of different CAR designs. We show that yeast is an alternative to conventional technologies (e.g. microbeads) and can provide higher activation control of clinically derived CAR T cells in vitro, relative to cancer cells. In summary, we present a customizable yeast-based platform for high-throughput characterization of CAR-T cell functionality and show potential applications within therapeutic T cells in clinical settings.
Insights
Researchers developed a novel yeast-based system to precisely control cancer cell antigen levels. This tool aids in optimizing chimeric antigen receptor (CAR) T cell therapy for better quality and safety in treating blood cancers.
Area of Science:
- Biotechnology
- Immunotherapy
- Synthetic Biology
Background:
- Chimeric antigen receptor (CAR) T cell therapy shows promise for hematological malignancies.
- Cancer cell antigen variability impacts CAR T cell therapy efficacy and safety.
Purpose of the Study:
- To develop an engineered yeast-based system for precise regulation of surface-antigen densities on simulated cancer cells.
- To provide a tool for controlled activation of CAR T cells and systematic assessment of antigen density effects.
Main Methods:
- Developed the Synthetic Cellular Advanced Signal Adapter (SCASA) system using engineered yeast.
- Utilized G protein-coupled receptor signaling to control cancer antigen densities on yeast.
- Demonstrated synthetic cellular communication between CD19-displaying yeast and human CAR T cells.
Main Results:
- The SCASA system allows precise regulation of antigen density for controlled CAR T cell activation.
- Yeast-based system demonstrated effective simulation of CD19+ cancer cells for CAR T cell characterization.
- Yeast platform provided superior activation control of CAR T cells compared to conventional methods in vitro.
Conclusions:
- The customizable yeast-based platform offers a novel approach for high-throughput characterization of CAR T cell functionality.
- This system has potential applications in refining therapeutic T cells for clinical settings.
- Engineered yeast serves as a viable alternative to traditional technologies for CAR T cell research.
Related Concept Videos
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:22Antigen Presenting Cells
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...