Ex-vivo Production of Regulatory B-Cells (Breg) for Use in Auto-immune Indications

Regulatory B-cells (Breg) play an important role in reducing autoimmunity and reduced levels of these cells are implicated in etiology of several auto-inflammatory diseases. Despite their impact in many diseases, their physiological inducers are unknown. Given that Bregs are a very rare B-cell, identifying factors that promote their development would allow in vivo modulation of Breg levels and ex-vivo production of large amounts of antigen-specific Bregs to use in immunotherapy for auto-inflammatory diseases.

The invention herein, is a method of ex-vivo production of Breg. The method of production involves treating isolated primary B cells or B cell lines with IL-35 to induce their conversion into IL-10- producing Breg. Using this method, B-regulatory cells can be produced in large quantity and used in a Breg-based therapy against autoimmune diseases including but not limited to uveitis and sarcoidosis.

Potential Commercial Applications: Competitive Advantages:
  • In vivo modulation of Breg levels
  • Supplement the low population of Breg in a patient suffering from an autoimmune disease where it is known that B-regulatory cell populations are severely reduced (i.e. uveitis)
  • Use in immunotherapy for the treatment of other autoimmune diseases such as multiple sclerosis, sarcoidosis, colitis, and arthritis.
  • There is no known biological or chemical agent that can induce Bregs ex-vivo.
  • This method produces large quantities of Bregs and can therefore aid in Breg-based therapy.
  • Pre-clinical mouse model data available that uses the Bregs to treat experimental autoimmune uveitis (EAU).

Charles Egwuagu (NEI)
Ren_Wi Wang (NEI)
Cheng-Rong Yu (NEI)

Intellectual Property:
US Application No. 61/637,915
PCT Application No. PCT/US2013/036175

Shen P, et al. PMID 24572363
Ding Q, et al. PMID 21821911
Carter NA, et al. PMID 21464089
Collison LW, et al. PMID 20953201
Kochetkova I, et al. PMID 20483737

Collaboration Opportunity:

The National Eye Institute, Molecular Immunology Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Ex-vivo Production of Regulatory B-Cells (Breg). For collaboration opportunities, please contact Alan Hubbs, Ph.D. at hubbsa@mail.nih.gov. To view the NEI collaborative opportunity announcement, click here.

Licensing Contact:
Yolanda Hawkins , Ph.D.
NIH Office of Technology Transfer
Email: hawkinsy@mail.nih.gov
Phone: 301-435-5170

OTT Reference No: E-036-2012/0

Updated: Apr-15-2014