Method to Modulate the Immune System Using Mesenchymal Stem Cells, Cytokines and Chemokines

Invention Summary:

Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into several types of tissue and are responsible for tissue repair and regeneration.  They are highly immunosuppressive.  It has been shown that MSCs can suppress T cell proliferation and cytokine production induced by mitogens or properly presented antigens.  The immunosuppressive capacity of MSCs offers great potential for the treatment of various autoimmune disorders, allergic reactions, transplant rejections, and cancer.  Most interestingly, MSCs can help successful engraftment of transplanted bone marrow and cells differentiated from embryonic stem cells or induced pluripotent stem (iPS) cells.  However, as the underlying mechanisms through which MSCs suppress immune reactions are largely unknown, the immunomodulatory potentials of MSCs have yet to be recognized.  Importantly, the clinical effects of MSCs vary significantly depending on the status of MSCs.  We believe that to modify MSCs with inflammatory cytokines prior to administration into patients would dramatically enhance the efficacy of these cells in clinical settings. The present invention is to establish a method to enhance MSC-mediated immunosuppression for clinical use with inflammatory cytokine-pretreatment, as well as provide a new source of immune adjuvants using gene modified MSCs. 

Researchers at Rutgers found that the immunosuppression was not an inherited property, but elicited by inflammatory cytokine, produced during an immune response. It was found that, in absence of inflammatory cytokines, MSCs lost their immunosuppressive effect, whereas addition of these factors primed MSCs to achieve a potent inhibitory function toward proliferation of activated T cells.  Importantly, the crucial role of inflammatory cytokines was verified by in vivo graft-versus-host disease (GvHD) studies. Interestingly, it was also revealed that gene-modified MSCs could reversely boost the immune response, owning to the secretion of a large amount of chemokines by MSCs.  Therefore, the present invention offers powerful suppressive and augmentative strategies to control the immune response.

Market Applications:

  • To develop kits with inflammatory cytokines to pretreat MSCs to augment their immunosuppressive effect, in prevention and treatment of various immune disorders such as multiple sclerosis, arthritis, lupus, sepsis, and GvHD.
  • To develop pharmaceutical reagents that block the immunosuppressive properties of tumor associated MSCs to enhance immunity to cancer, especially in combination with tumor immune therapy protocols.
  • To develop vaccines and cancer immunotherapies using gene-modified MSCs as immune adjuvants.

Intellectual Property & Development Status:

Published PCT application: PCT/US2009/0202479

Rutgers ID: S06-75
Category(s):
Life Sciences
Therapeutics
Contact:
Shan Wan
Senior Licensing Manager
(848) 932-4468
shanwan@rutgers.edu
Inventors:
Yufang Shi
Guangwen Ren
Liying Zhang
Keywords:
Infectious Disease/Immunology
Oncology
Stem Cells