Human Lymphoid Organ-Derived Suppressive Stromal Cells for Autoimmune and Inflammatory Disease Treatment

Project Overview

• Dana-Farber scientists have invented alternative pharmaceutical preparations and methods for suppressing an immune response by isolation and administration of isolated lymphoid tissue-derived suppressive stromal cells (“LSSCs”).
• These LSSCs represent a promising therapeutic treatment for autoimmune and inflammatory disease, including but not limited to severe graft-versus-host disease, acute septic shock, rheumatoid arthritis, multiple sclerosis, psoriasis, and inflammatory bowel disease.
• The technology is available for licensing.

Technology

Unlike other immunosuppressive stromal cell populations, such as mesenchymal stromal cells, LSSCs can directly attract immune cells such as T cells as well as suppress them. The isolated LSSCs of the present invention exhibit potent and effective immunosuppression in vitro and in vivo, making them a promising therapeutic treatment for autoimmune and inflammatory disease, including but not limited to severe graft-versus-host disease, acute septic shock, rheumatoid arthritis, multiple sclerosis, psoriasis, and inflammatory bowel disease. 

The technology developed by Dana-Farber scientists covers methods for isolating, purifying, and expanding isolated LSSC’s ex vivo in a commercially applicable manner as well as uses of isolated LSSCs, particularly therapeutic administration to suppress autologous, allogeneic, and xenogeneic immune responses.

The isolated LSSCs comprise fibroblastic reticular cells (“FRCs”) which are shown to suppress the immune response in vivo and in vitro using novel mechanisms, and are shown to significantly reduce early lethality in mice with various diseases or pathologies having an unwanted inflammatory component. As one example, unlike mesenchymal stromal cells administered as an allogeneic therapy, the invention provided significant survival benefit in mouse models of sepsis. 

In one example, mechanistic studies were performed, e.g., by isolating two cell type subpopulations (PDPN+ and PDPN-) found within the human lymphoid tissue-derived stromal population and culturing them with purified blood-derived T cells. T cells were labelled with Carboxy Fluoroscein Succinimidyl Ester (CFSE), which is diluted when a cell divides, and activated. T cells stimulated in the presence of LSSCs showed less CFSE dilution, showing that human LSSCs halt the division of pre-activated allogeneic T cells. 

Benefits of the technology:

• Immunosuppressive drugs currently approved for treatment of chronic inflammatory disease carry significant side effects, including risks of morbidity, and must be frequently administered.
• LSSCs as compared to mesenchymal stromal cells, are known to directly attract immune cells. This claimed invention shows that LSSC’s are potent immunosuppressors and have the combined ability to both attract and inhibit T cells. 

Applications

This invention could be used in patients suffering from an autoimmune disease. It could also prevent a rejection in transplant patients.

Opportunities

Dana‑Farber is interested primarily in licensing opportunities for this technology.