Escape tag

In the unlikely case that our therapeutic cells escape from the capsules and to prevent their dissemination through the body we designed a safety mechanism that would enhance the recognition and destruction of the escaped therapeutic cells by the innate immune system.

We introduced an escape tag that labels the cells with a surface protein that alerts natural killer cells of the host organism to recognize and destroy cells.

HEK293 cells expressing MICA protein were efficiently killed by human NK cells.

We considered several variants to ensure destruction of escaped cells such as:

1. quorum sensing which would provide the survival signal only for cell clusters within microcapsules,
2. conjugation of microcapsule material with a ligand for a receptor that provides a survival signal,
3. activation of apoptosis for escaped cells when they encounter the extracellular matrix and
4. tagging cells for the recognition and destruction by the cells of the immune system.

After considering many factors we selected the immuno-tagging variant because of its elegant simplicity and since it seems less sensitive to the spontaneous loss of the constructs and leaky apoptosis than other options.

The MICA/NKG2D system

Though our microencapsulation system is designed in such a way that the capsules are permeable only to nutrients, signalling molecules and produced protein therapeutics, we cannot completely exclude the possibility that some cells could escape from the microcapsules, e.g. due to mechanical damage. We designed a safety mechanism that would ensure that the escaped therapeutic cells could not survive outside microcapsules because of enhanced recognition by the innate immune system.