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HMGN Polypeptides as Immune Enhancers and HMGN Antagonists as Immune Suppressants

Posted May 31 2012 8:00pm

Description of Invention:
HMGN polypeptides are multidomain proteins known to function by binding DNA to regulate the transcription of certain genes inside cells. However, when a HMGN polypeptide is released extracellularly, it distinctly acts as a potent activator of the immune system. Because of this activity, it has potential use as a biological therapeutic for stimulating an immune response as well as a promising target for antagonist drugs to suppress a pathological inflammatory response.

Secreted HMGN acts as a potent recruiter and activator of dendritic cells, the cell principally responsible for initiating the immune response. Furthermore, it enables dendritic cells to preferentially induce a Th1-type T lymphocyte response that leads to enduring cellular immunity. Therefore, HMGN has potential use as a clinically effective immunoadjuvant for use in vaccines against tumors and many intracellular pathogens.

Investigators at the National Institutes of Health have developed compositions and methods for using HMGN and its derivatives as immunoadjuvants in combination, as mixtures or as chemical conjugates, with microbial or tumor antigens. HMGN has the advantage of being gene encoded so it can be fused to an antigen gene to produce recombinant fusion proteins or administered as a DNA vaccine. Conversely, HMGN could be exploited as a drug target to treat diseases that would benefit from shifting away the Th1-type immune response towards a Th2-type or humoral immune response. This would be beneficial for treatment of parasitic infections and inflammatory or autoimmune disorders.

Applications:
  • As an immunostimulatory adjuvant to increase efficacy of preventive or therapeutic vaccinations against microbes or cancers
  • As an attractant and activator of dendritic cells
  • Antagonist drug development for suppressing Th1-type response


Advantages:
  • Less adverse effects expected compared to current immunoadjuvants since HMGN is produced by the human body
  • Highly effective polarizer of the immune response towards Th1-type immunity


Development Status:
Pre-clinical data available

Inventors:
De Yang (NCI)


Patent Status:
HHS, Reference No. E-185-2008/0
US, Application No. 12/509,088 filed 24 Jul 2009
US, Application No. 61/083,781 filed 25 Jul 2008


Relevant Publication:
  1. Presently, none related to this invention


Collaborative Research Opportunity:
The National Cancer Institute Laboratory of Molecular Immunoregulation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HMGN1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


For Licensing Information Please Contact:
Surekha Vathyam Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: vathyams@mail.nih.gov
Phone: 301-435-4076
Fax: 301-402-0220


Ref No: 1880

Updated: 06/2012

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