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HMGN Polypeptides as Immune Enhancers and HMGN Antagonists as Immune Suppressants

19:00 EST 1 Feb 2009 | NIH

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.

IC: 
NCI
NIH Ref. No.: 
E-185-2008/0
TAB No: 
TAB-1880
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
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
Development Status: 

Pre-clinical data available

Provider Technology ID: 
1880
Updated On: 
Aug 3, 2017
Provider Classifications: 
Date Published: 
Monday, February 2, 2009
Patent Application: 
61/083,781
12/509,088
15/191,000
13/533,492
Publications: 
2016-03-22 00:00:00
2016-03-22 00:00:00
Patent Authority: 
US
US
US
US
Patent Number: 
8,227,417
9,567,566
Licensing Contacts: 
LPM Address: 
  --
United States
Lead Inventor: 
Inventor IC: 
NCI
Inventor Lab URL: 
https://ccr.cancer.gov/de-yang
LPM FIrst Name: 
Rose
LPM Last Name: 
Freel
LPM Address: 
8490 Progress Drive, Riverside 5, Suite 400
LPM City: 
Frederick
Inv Is lead: 
LPM Zip: 
21701
LPM State: 
MD
LPM Phone: 
301-624-1257
LPM Suffix: 
Ph.D.
LPM Organization: 
NIH Office of Technology Transfer
LPM Fax: 
301-631-3027
DTDT Classification: 
Cancer
Therapeutics
Immunoconjugates
Other
Vaccines
Immunomodulators and Immunostimulants
DTDT Description: 
Cancer
Cancer - Therapeutics
Cancer - Therapeutics - Immunoconjugates
Cancer - Therapeutics - Immunoconjugates: Other
Cancer - Therapeutics: Vaccines
Cancer - Therapeutics: Immunomodulators and Immunostimulants
Pat Filing Date: 
2008-07-25
2009-07-24
2016-06-23
2013-06-26
Patent Issue Date: 
2012-07-24
2017-02-14
Publication Link: 
https://www.ncbi.nlm.nih.gov/pubmed/22184635
Publication Caption: 
PMID 22184635
Publication Title: 

Yang D, et al.

Disease Area Term: 
Collaboration Sought: 
Yes
Institute or Center: 
Collaboration Opportunity: 

The National Cancer Institute, Laboratory of Molecular Immunoregulation, seeks parties interested in collaborative research to co-develop polypeptides or antagonists for immune response regulation. Please contact John D. Hewes, Ph.D. at 240-276-5515 or john.hewes@nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

E Number Only: 
E-185-2008
Inventor First Name: 
De
Inventor Last Name: 
Yang

Original Article: HMGN Polypeptides as Immune Enhancers and HMGN Antagonists as Immune Suppressants

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