Logic-gated CARs: a unified framework for programmable cell-based delivery systems

Area of Science:

• Immunology
• Biotechnology
• Synthetic Biology

Background:

• Logic-gated chimeric antigen receptors (CARs) enhance engineered immune cells' ability to process multiple inputs.
• Diverse CAR designs and terminology hinder cross-study comparisons and development.

Purpose of the Study:

• To present a unified framework for classifying logic-gated CARs based on Boolean logic and signal integration.
• To compare existing logic-gated CAR systems and summarize their clinical translation.

Main Methods:

• Classification of CARs using Boolean logic (YES, OR, AND, INHIBIT, sequential, hybrid).
• Comparison of CAR systems based on computational logic, molecular mechanisms, reversibility, modularity, and clinical translatability.

Main Results:

• A systematic framework categorizes logic-gated CARs into distinct Boolean logic architectures.
• Analysis highlights differences in design principles, mechanisms, and clinical potential across CAR types.

Conclusions:

• The proposed framework aids in understanding, designing, and translating next-generation logic-gated CAR therapies.
• Standardized classification promotes clearer communication and accelerates advancements in programmable immune cell therapies.