Harnessing the power of therapeutic human cells
A new treatment modality
For many years, researchers have worked towards implanted cell-based treatments as replacement therapies for severe chronic diseases. However, this approach suffers from a critical limitation: a patient’s immune system will recognize donor cells as foreign and then destroy them, unless the patient is given immunosuppressant drugs. Use of such drugs on a long-term basis is associated with significant risks including infection and cancer. Sigilon Therapeutics was founded to address these challenges and deliver cell-based therapeutics to patients with chronic disease.
This challenge partly explains why cell-based therapeutic implants are not yet more widespread. It also underscores the tremendous potential of Sigilon’s key innovation: The Shielded Living Therapeutics™ platform harnesses the power of therapeutic human cells without inducing an immune response.
The Shielded Living Therapeutics™ platform
4. Functional Cure
Sigilon has developed proprietary engineered human cells that:
- Express high levels of desired protein(s)
- Survive well in an encapsulation environment
- Can be produced at large scale
- Are similar to cells previously used in clinical applications
- Provide the ability to easily insert new gene expression cassettes for different applications
Part of Sigilon’s Shielded Living Therapeutics™ technology is our proprietary Afibromer™ matrix, which exhibits ideal properties for housing therapeutic cells and for the avoidance of fibrosis. Building upon foundational discoveries made at MIT, Sigilon has developed this matrix to be a super-biocompatible material that can remain in the body while generating minimal fibrosis or immune rejection.
Shielded Living Therapeutics™ products are placed in the abdomen via a brief laparoscopic procedure. This minimally invasive approach makes 2-4 small abdominal incisions and then the capsules are infused into the abdominal cavity. Other sites in development include subcutaneous, ocular and CNS.
4 Functional Cure
Our Shielded Living Therapeutics™ products contain engineered human cells that can either systematically deliver proteins at a constant rate or be programmed to respond to changing conditions (e.g., flare-ups that are characteristic of certain autoimmune diseases) or fluctuating levels of circulating factors such as glucose (e.g., conditions relevant to the treatment of diabetes).
Synthetic biology tools and programmable genetic circuits create new possibilities for engineering cells to sense changing conditions and respond appropriately. By combining such “sense and respond” cells with our Afibromer™ matrix, Sigilon can invent Shielded Living Therapeutics™ products with the potential to act as “smart” medicines inside the body for the treatment of complex and serious chronic diseases.
We create novel, engineered human cells that we encase in a proprietary immune-shielding biocompatible matrix and place in the body to provide potential functional cures for chronic diseases.
In experimental animal models, our Shielded Living Therapeutics™ products have resisted fibrosis for 12 months or more. Assuming this success can be repeated in humans, Shielded Living Therapeutics™ products could generate and secrete the natural biomolecules a patient needs over long periods of time, even years, maintaining constant therapeutic protein replacement. This goes beyond convenience and adherence and is expected to produce superior longer-term patient outcomes.
Shielded Living Therapeutics™ products capture benefits beyond existing therapies
In addition to our proprietary compound used in the Afibromer™ matrix, we have developed a proprietary library of Afibrotek™ compounds, which can be used to modify any biomaterial to prevent the foreign body response often seen when medical devices are placed into a patient. We have demonstrated the effectiveness of these Afibrotek™ compounds on a range of biomaterials which are used in many medical devices.
March 30, 2020 | Nature Biomedical Engineering | A Retrievable Implant for the Long-Term Encapsulation and Survival of Therapeutic Xenogeneic Cells
Winter 2019-2020 | Hemophilia Federation of America | Hemophilia Federation of America’s 2019-20 Special Dateline Federation Magazine: Emerging Therapies
August 13, 2018 | Nature Biomedical Engineering | Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques
July 30, 2018 | Nature Biomedical Engineering | Reduction of measurement noise in a continuous glucose monitor by coating the sensor with a zwitterionic polymer
April 12, 2018 | Cell Stem Cell | Evolving Industry Partnerships and Investments in Cell and Gene Therapies
April 2, 2018 | PharmTech | Future Therapies Using Implanted Engineered Cells as Protein Factories
December 11, 2018 | Nature Biomedical Engineering | Coated glucose sensors dodge recalibration
March 20, 2017 | Nature Materials | Colony stimulating factor-1 receptor is a central component ofthe foreign body response tobiomaterial implants in rodents and non-human primates
January 25, 2016 | Nature Medicine | Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice
January 25, 2016 | Nature Biotechnology | Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates
May 18, 2015 | Nature Materials | Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates