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Optimized Expression of IL-12 Cytokine Family

Posted May 05 2010 5:00pm

Description of Invention:
The IL-12 family of cytokines (IL-12, IL-23, and IL-27) has an important role in inflammation and autoimmune diseases. IL-12 is produced by macrophages and dendritic cells in response to certain bacterial and parasitic infections and is a powerful inducer of IFN-gamma production. IL-23 is proposed to stimulate a subset of T cells to produce IL-17, which in turn induce the production of proinflammatory cytokines that lead to a protective response during infection. IL-27 appears to have duel functions as an initiator of TH1-type (cellular immunity) immune responses and as an attenuator of immune/inflammatory responses.

The present inventions provide methods for improved expression of multimeric proteins by engineering different ratios of the subunit expression units in a cell or upon expression from a multi-promoter plasmid having different strength promoters. The inventors have improved the levels and efficiency of expression of the IL-12 family of cytokines, which includes IL-12, IL-23, and IL-27, by adjusting the transcription and translation of the alpha and beta subunits that comprise the heterodimeric proteins. Optimal ratios of expression for the two (2) subunits were determined for IL-12, IL-23, and IL-27.

  • Tumor treatment
  • Anti-viral therapy
  • Anti-inflammatory therapy

Increased expression and stability of in vitro expressed IL-12, IL-23 and IL-27 cytokines

Development Status:
In vitro data and data in animal models can be provided upon request.

George N Pavlakis (NCI)
Barbara K Felber (NCI)

Patent Status:
HHS, Reference No. E-192-2008/1
PCT, Application No. PCT/US09/043481 filed 11 May 2009 , which published as WO 2009/140206 on 19 Nov 2009

Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The Center for Cancer Research, Human Retrovirus Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize delivery of cytokines of the IL-12 family in cancer and other indications. Please contact John D. Hewes, Ph.D. at 301-435-3121 or for more information.

Cancer - Therapeutics
Infectious Diseases
Infectious Diseases - Vaccines
Internal Medicine
Internal Medicine - Therapeutics

For Additional Information Please Contact:
Kevin Chang Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-5018
Fax: 301-402-0220

Ref No: 2036

Updated: 05/2010

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