Safety mechanisms

Capsule degradation - at the end of the therapy production of the secretory alginate lyase is induced which degrades the microcapsules, allowing immune cells to reach and clean up the therapeutic cells.

Termination tag - our therapeutic cells constitutively produce thymidine kinase. At the end of the therapy the prodrug ganciclovir is added which is transformed into a toxic compound that initiates cell apoptosis only in therapeutic cells that constitutively produce thymidine kinase.

Escape tag - therapeutic cells express MICA protein tag at their surface that has strong affinity for the receptor NKG2D expressed by natural killer cells. In case the therapeutic cells escape form the alginate capsule the MICA protein at their surface recruits the natural killer cells that induce their killing.

Figure 1. Overview of the designed safety mechanisms for therapeutic use of microencapsulated engineered cells.

Inactivation and elimination of the cellular devices