Chimeric antigen receptor (CAR) T cell therapy involves the introduction of genetically modified T cells to a patient with the purpose of identifying and targeting cancer cells. Development of successful CAR T cell therapies requires:
- >> Appropriate antigen targeting
>> CAR optimization
>> Predictive potency assessment
>> Immune cell exhaustion/persistence evaluation - To address these limitations and develop a safe and robust immune cell product, our live-cell analysis platforms can be used to measure phenotype, potency, and persistence of CAR T cells.
T Cells and CAR T Cells
T cell receptors (TCRs) in unmodified T cells detect antigens presented by MHC while chimeric antigen receptors (CARs) in CAR T cells recognize antigens expressed by the target cell.
Structure of a CAR
- Signaling domain — stimulates the activation and proliferation of the T cell
- Transmembrane domain — anchors the CAR to the membrane
- Antigen recognition domain — recognizes and binds to the target cell antigen
CAR T Immunotherapy Assays
-
CAR Optimization with Imaging>
-
Assess specificity of a CAR T cell-mediated response >
-
Measure efficacy against solid tumor spheroids >
-
Evaluate CAR T cell exhaustion>
-
Measure CAR T cell-mediated cytotoxicity>
-
Application Note: Development of a functional cardiotoxicity assay for evaluating the safety of cell therapies>
CAR optimization is critical for effective in vitro immuno-oncology assay development. The Omni live-cell imaging system was used to compare the killing of different CAR constructs and showed that cell death was observed in a dose-dependent manner.
Confluency of RFP-labeled cancer cells after the addition of CAR T cells is measured with the Omni platform. Two different CAR constructs were compared across E:T ratios and Construct 1 showed a greater potency across all ratios.
“Great results!”
Quantitative data with a convenient mobile app. The Maestro Z provides a quantitative measurement of CAR-T cell-mediated cytotoxicity. The system is very easy to use, and it's powerful to see CAR-T cell killing profiles over time. The number of experiments you can run continuously with majority hands-off time is incredible. The mobile app is also great for making decisions about when to come into the lab when to add effectors, and so on.
- Heather Lin. Emory University, Georgia, USA
