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Agonistic Human Monoclonal Antibodies Against DR4

Posted Mar 14 2011 8:00pm

Description of Invention:
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been recognized as promising targets for cancer treatment. Therapeutics targeting TRAIL and its receptors are not only effective in killing many types of tumors but they also synergize with traditional therapies, and show efficacy against tumors that are otherwise resistant to conventional treatments.

The researchers at the NIH have developed two human monoclonal antibodies (mAbs) that bind to death receptor 4 (“DR4”). One of the mAbs is agonistic and inhibits the growth of ST486 cells with IC50 of about 10nM. The two mAbs were selected from a human phage-displayed Fab library by panning against a recombinant DR4 extracellular domain. Therefore the two mAbs are fully human. These antibodies could have considerable potential as cancer therapeutics alone or in combination with other drugs. Further, these antibodies could be used as a research tool for the study of DR4.

Applications:
  • The DR4 antibodies could be promising candidate cancer therapeutics. Ongoing phase I and II clinical trials with mostly DR5-targeting agonistic antibodies have indicated that they are safe and could be efficacious for certain indications.
  • DR4 is expressed in a broad range of solid tumors and malignancies and therefore antibodies to DR4 would be also useful reagents to study this expression.


Development Status:
Pre-clinical proof of principle.

Inventors:
Dimiter S Dimitrov (NCI)


Patent Status:
HHS, Reference No. E-158-2010/0
US, Application No. 61/355,349 filed 16 Jun 2010


Relevant Publication:
  1. Feng Y, Xiao X, Zhu Z, Dimitrov D. Identification and characterization of a novel agonistic anti-DR4 human monoclonal antibody. MAbs. 2010 Sep-Oct;2(5):565-570. [ PubMed: 20581445 ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Cancer Institute, Membrane Structure and Function Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize topic of invention or related laboratory interests. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Cancer
Cancer - Therapeutics
Cancer - Research Materials



For Licensing Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220


Ref No: 2241

Updated: 03/2011

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