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A Novel, Inhibitory Platelet Surface Protein (TREM Like Transcript, TLT-1): New Target for the Treatment of Cancer, Infectious D

Posted Jun 15 2010 5:00pm

Description of Invention:
Triggering Receptors in Myeloid Cells (TREM) recently were discovered to modulate innate and adaptive immunity. Specifically, TREM1 amplifies the response to sepsis in innate immunity by activating neutrophils and other leukocytes; and TREM2 potentiates dendritic cell maturation in adaptive immunity.

This invention describes a novel, inhibitory platelet surface protein known as TREM like Transcript (TLT-1). TLT-1 is the first inhibitory receptor discovered to reside within the TREM gene locus. Structurally, TLT-1 also possesses inhibitory domains that indicate this regulatory function. TLT-1 is highly expressed in peripheral blood platelets and may modulate many other types of myeloid cells. Additionally, the invention describes specific, human, single chain antibodies (scFvs) that recognize TLT-1.

Applications:
  • This discovery implies the receptor has an important regulatory role in both innate and adaptive immunity.
  • TLT-1 is a potential therapeutic target for thrombosis and other platelet-associated disorders, as well as immune disorders, cancer, septic shock, infectious disease, stroke, heart disease, myocardial infarction, vascular disorders.
  • Detection of soluble TLT-1 in patient plasma suggests the protein is a marker of ongoing coagulopathies.
  • Defective platelet aggregation in TLT-1 null mice confirms a role for the protein in regulation of thrombosis associated with inflammation.


Advantages:
  • In vitro proof of concept data available - Three of the anti-TLT-1 scFvs inhibit thrombin-induced aggregation of human platelets in a dose-dependent manner.
  • Complete human origin of these antibodies suggests negligible immunogenicity and minimizes the problem of adverse immune responses in human therapy.
  • Target validation is complete. TLT-1 null mice demonstrate defects in platelet aggregation with no gross bleeding defect.


Development Status:
In vitro experiments completed. Target validation with null mice completed. In vivo animal studies with scFv are currently ongoing.

Inventors:
Toshiyuki Mori (NCI)


Patent Status:
HHS, Reference No. E-177-2006/0
US, , Patent No. 7,553,936, Issued 30 Jun 2009


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Cancer Institute's Molecular Targets Development Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antibodies that react specifically with TLT-1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Cancer
Cancer - Diagnostics
Cancer - Therapeutics
In-vivo Data
In-vitro Data



For Additional Information Please Contact:
Betty Tong Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: tongb@mail.nih.gov
Phone: 301-594-6565
Fax: 301-402-0220


Ref No: 1682

Updated: 06/2010

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