Psoriasis Management: Automatically adapting Treatment based on Disease activity

Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis.

Schukur L, Geering B, Charpin-El Hamri G, Fussenegger M.

Sci Transl Med. 2015 Dec 16;7(318):318ra201. doi: 10.1126/scitranslmed.aac4964.

• Psoriasis is a chronic auto-inflammatory condition which has a genetic and environmental cause. Because of this the disease goes through phases of improvement and worsening (flaring) and the treatment is NOT always adapted to the current disease activity
• There is a way to do this via specialized “Theranostic cells”. Simply defined it is an implantable device containing cells which gauge psoriasis disease activity through measurement of cytokines.

• In this Swiss study (Basel) implants* were introduced into the peritoneum of mice and psoriasis-like lesions were induced with imiquimod.
• Disease activity was measured by engineered human embryonic kidney cells which detected the combination of the psoriasis-associated cytokines TNF and IL-22 levels
• After processing, the designed cells are activated to release matched levels of cytokines IL-4 and IL-10: these are anti-inflammatory cytokines which subsequently allow the control of psoriasis.

How do these engineered Stem Cells work ?

-TNF receptor signaling in the converter cell is artificially coupled to IL-22 receptor (Il-22R).

-the detection of TNF drives the expression of a functional IL-22R, which is required to sense the presence of IL-22

-The IL-22R signaling pathway itself is rewired to a transcription factor called signal transducer and activator of transcription 3 (STAT3), and a synthetic STAT3-responsive promoter drives the expression of IL-4 and IL-10

• These implants are specific to psoriasis, and are not influenced by other inflammatory processes or infections (bacterial, viral).
• Results show that these implants stopped acute flares of psoriasis, improved the lesions and contributed to normal skin tissue structure.

• This suggests that psoriasis as other chronic conditions could be efficiently managed by using this method. Still in practice there are still many hurdles which include:

1. type of cells to be used for the synthetic design in humans (most likely autologous
2. cells)
3. the differences in treatment responses in individual patients
4. the dosing performance overall and for each individual patient
5. the localization of implantation
6. the possibility to remove the implant easily

*alginate-based biomaterial with an optimal pore size for cytokine diffusion, but lacking immunogenicity [the biomaterial had been successfully used in clinical trials of type I diabetes]

Article selection: Prof Dr Jean-Hilaire Saurat – dermatologist. Geneva, Switzerland