Therapeutic Antitumor Combination Containing TLR4 Agonist HMGN1


Immune checkpoint inhibitors (e.g. CTLA-4, PD-L1) have recently shown significant promise in the treatment of cancer.  However, when used alone, these checkpoint inhibitors are limited by the absence or repression of immune cells within the targeted cancer.  For those cancers associated with these limited immune systems, there remains a need for effective therapies.  Agents capable of recruiting and activating immune cells to these types of cancers could extend the overall and complete response rates of combination therapies within the immunooncology domain. 

Researchers at the National Cancer Institute (NCI) have developed a combination therapy capable of recruiting and activating immune cells for the treatment of cancer.  This therapy incorporates, HMGN1, an alarmin, which recruits immune cells using its chemotactic-induction capabilities, and activates dendritic cell maturation via its TLR4 agonism. The combination of HMGN1 with TLR7/8 agonism and immune-checkpoint inhibition has been tested in xenograft models. In those models, mice bearing ~1cm tumors were successfully treated and resistant to re-challenge. Development of this combination continues and is available for in-licensing and co-development. 



Potential Commercial Applications: Competitive Advantages:
  • Treatment of solid tumors
 
  • Superior to TLR7/8 agonism and/or checkpoint inhibitors alone
  • No need for the exogenous inclusion of tumor-associated antigen


Development Stage:
Pre-clinical (in vivo)

Related Invention(s):
E-185-2008
E-269-2016


Inventors:

Joost Oppenheim (NCI)  ➽ more inventions...

De Yang (NCI)  ➽ more inventions...


Intellectual Property:
Application No. 62/355,134

Publications:
Nie Y, et al. Development of a Curative Therapeutic Vaccine (TheraVac) for the Treatment of Large Established Tumors.  PMID 29079801
Han Z, et al. Therapeutic vaccine to cure large mouse hepatocellular carcinomas.  PMID 28881713

Collaboration Opportunity:

Licensing and research collaboration


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-069-2016
Updated: Oct 15, 2018