Implantation of cells designed to sense the presence of proinflammatory cytokines and subsequently produce and deliver anti-inflammatory molecules prevented flares of psoriasis in mice, according to Lina Schukur of the department of Biosystems Science and Engineering, ETH Zurich, in Basel, Switzerland, and associates.
The investigators designed and engineered human cells that they explain “sequentially detected elevated TNF [tumor necrosis factor] and IL-22 [interleukin-22] levels from a psoriatic flare and, in response, produced therapeutic doses of IL-4 [interleukin-4] and IL-10 [interleukin-10].” TNF and IL-22 are proinflammatory cytokines, which have been found to be upregulated in patients with active psoriasis; and IL-4 and IL-10 are immunomodulatory cytokines that have been shown to induce rapid improvements in people with psoriasis in phase II clinical trials, they noted.
The researchers implanted these designer cells in mice with psoriasis-like lesions, which showed that this “antipsoriatic cytokine converter network” was able to improve skin lesions “and restore dermal tissue morphology.” They also found that the cells were responsive in blood samples from psoriasis patients, which suggested that the cytokine converter “is sufficiently sensitive to detect circulating TNF and IL-22 in humans.”
“These synthetic circuits, which program designer cells to process complex metabolic information, open the door to autonomously prevent, attenuate, or reset acute or chronic medical conditions without constant injections of drugs or cumbersome dosing schedules, and thus provide a new opportunity for personalized medicine,” the investigators wrote.
An editor’s summary of the study states that, “in demonstrating that the converter cells were responsive to blood from psoriasis patients, the authors suggest that synthetic biology may be ready to autonomously flip therapeutic switches in people and later take on other diseases with defined disease indicators.”
The full study, published on Dec. 16, 2015, is available in Science Translational Medicine at http://stm.sciencemag.org/content/7/318/318ra201.