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CAR Activation Results
CAR Activation Results
We were able to activate PEbody CAR at antibody concentration 1nM, 3nM and 5nM and the activation level did not vary significantly. This result suggests that the antibody might already be saturated at 1nM and for future optimization, lower antibody concentration can be tested.
The positive control, CD19 CAR, has higher activation due to a higher CAR expression level. Given the inconsistent CAR expression level, more tests are needed before a conclusion can be drawn.
Killing Assay Results
Killing Assay Results
Plain PBMC cells unexpectedly showed high killing efficacy. We believe this result is due to poor cell conditions (low cell viability and low PEbody CAR expression) prior to the experiment.
Due to the time constraint, we were not able to repeat this experiment. However, future repeats are expected after the protocol is updated with more quality control steps.
Conclusion
Conclusion
The PEbody CAR T cells can be activated to trigger downstream signaling pathways for tumor killing. However, the killing efficacy of the PEbody CAR remains to be further tested. Moreover, the co-culture conditions need further optimization for better performance of the PEbody CAR.
Future Work
Future Work
In Vivo Experiments
In Vivo Experiments
We plan to move onto a mouse model once we have optimized our PE CAR T cell performance in vitro. CAR T cell therapy has traditionally struggled in treating solid body tumors effectively, so an in vivo model would be a good way to test the performance for solid tumors.
Activation Control Gate
Activation Control Gate
We would like to incorporate an activation control gate that responds to an external stimulus, such as an ultrasound impulse. This would enable spatial and temporal control over CAR T cell activation, thereby reducing off-target toxicity and preventing premature exhaustion in vivo.
PD-1/PD-L1 Inhibitor
PD-1/PD-L1 Inhibitor
Solid tumors are particularly difficult to treat with CAR T cell therapy due to the hostile microenvironment they produce. One component of this microenvironment is PD-L1, which, when it binds to the PD-1 receptor on a T cell, de-activates the T cell and prevents further immune responses. By including a PD-1/PD-L1 inhibitor, we can protect the CAR T cell from the microenvironment and increase cell efficacy.
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