Logic-gated CAR Construction Service

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Logic-gated CARs represent a sophisticated evolution of the conventional CAR-T therapy. These CARs are engineered with advanced molecular switches, allowing them to be activated in a controlled and precisely regulated manner. At Creative Biolabs, our Logic-Gated CAR Construction Service leverages these state-of-the-art advancements to create tailored solutions for our clients.

Logic-Gated CAR Types

1. AND-Gate CARs

AND-Gate CARs require the presence of multiple antigens to trigger T-cell activation. These CARs demand the simultaneous engagement of two or more antigenic targets, effectively enhancing the specificity of target recognition. This is particularly advantageous in scenarios where single-antigen targeting might lead to therapy escape due to antigen loss.

Figure 1. The scheme of IVT mRNA CAR T therapy in cancer patients. (Savanur, et al., 2021) Figure 1 Schematic representation of selected logic AND gate strategies.¹

2. OR-Gate CARs

In contrast, OR-Gate CARs are designed to activate T-cells when they encounter any one of the multiple target antigens. This flexible approach ensures that the CAR-T cells remain active as long as they identify at least one antigen, making them adaptable to the heterogeneity of tumor cell populations.

Figure 2 Schematic representation of selected logic OR gate strategies.²

3. NOT-Gate CARs

NOT-Gate CARs operate inversely by suppressing T-cell activity upon recognizing specific antigens. This design can be valuable in mitigating the adverse effects of CAR-T therapy on healthy tissues, reducing toxicity, and enhancing safety profiles.

Figure 3 Schematic representation of selected logic NOT gate strategies.¹

Logic-Gated CAR Advantages

Enhanced Precision
Logic-gated CARs epitomize precision medicine by targeting cancer cells with unmatched specificity. Their ability to discriminate between multiple antigenic profiles ensures that only cancerous cells are eradicated, sparing healthy tissues from harm.
Reduced Toxicity
By minimizing off-target effects and collateral damage to non-cancerous cells, Logic-Gated CARs substantially decrease the risk of toxicity associated with CAR-T therapy. This enhanced safety profile translates to a more favorable patient experience.
Overcoming Antigen Escape
AND-Gate CARs offer a robust solution to the challenge of antigen escape, a phenomenon where cancer cells lose the target antigens over time. By requiring multiple antigen engagement, these CARs effectively counteract this escape mechanism.
Adaptability to Tumor Heterogeneity
OR-Gate CARs are a powerful tool against tumors with heterogeneous antigen expression.
Improved Safety with NOT-Gate CARs
NOT-Gate CARs enhance safety by deactivating T-cells in the presence of specific antigens. This feature is instrumental in mitigating autoimmune responses and off-target cytotoxicity.

Customized CAR Design Service

At Creative Biolabs, we understand the importance of flexibility in CAR-T therapy. With our team of expert scientists and cutting-edge technologies, we can tailor Logic-gated CARs to your exact specifications. Whether you require a unique Boolean logic configuration or want to incorporate additional safety features, our service ensures that your CAR-T therapy aligns perfectly with your patients' needs.

References

Savanur, et al. "Implementing logic gates for safer immunotherapy of cancer." Frontiers in Immunology 12 (2021): 780399.
Han, Xiao, et al. "Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy." Journal of hematology & oncology 12 (2019): 1-10.