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Cells and Nanoparticles with Altered Protein Expression Patterns Useful for the Modulation of T Cell Activity for Immunotherapy

Posted Aug 04 2011 8:00pm

Description of Invention:
NIH scientists have developed human cells and nanoparticles to enhance immunotherapy. Specifically, researchers have identified that cells or nanoparticles expressing a high temperature requirement serine peptidase 1 (HtrA1) activator and/or a cytokine-induced Src homology 2 protein (CIS) inhibitor are capable of increasing T cell activity. These compositions can be used primarily in T cell immunotherapy against various cancers and infectious diseases where enhanced T cell activity is beneficial. Conversely, cells or nanoparticles that express a HtrA1 inhibitor and/or a CIS activator can suppress T cell activity. These compositions can be utilized to treat various auto- or alloimmune diseases and can be used to prevent transplant rejections.

HtrA1 (also known as L56, ARMD7, ORF480, and PRSS11) is a serine protease that is known to inhibit the TGF-beta family proteins. CIS (also known as G18, SOCS, CIS-1, and CISH) is a member of the suppression of cytokine signaling (SOCS) family of proteins and inhibit the JAK/STAT signaling pathways. CIS acts to inhibit HtrA1 and repress cell activation targets. Immunotherapy, although an effective treatment strategy, sometimes fails when cells lose activity. T cells adoptively transferred into patients where CIS is inhibited and/or HtrA1 is activated should maintain their activity and lead to more successful adoptive T cell transfers.

Applications:
  • Immunotherapy for cancer or infectious diseases using human cells or nanoparticles expressing an HtrA1 activator and/or a CIS inhibitor
  • Therapeutic for treating autoimmune diseases using human cells and or nanoparticles expressing an HtrA1 inhibitor and/or a CIS activator
  • Agents expressing an HtrA1 inhibitor and/or a CIS activator to prevent organ, tissue, or cell transplant rejection and treat alloimmune diseases, such as graft-versus-host disease
  • Components of a combination therapy to increase or suppress T cell activity in a patient


Advantages:
  • Some patients do not respond to T cell immunotherapy due to lack of cell persistence, survival, or activity as well as for other poorly understood reasons. Modifying HtrA1 and CIS in currently existing T cell immunotherapies should increase the success rate of these therapies by increasing the persistence and survival of the infused cells.
  • T cells can become "exhausted" as they mature following activation by target antigen. Cells with altered expression of HtrA1 and/or CIS may be able to avoid exhaustion after repeated activation.


Development Status:
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Douglas C Palmer (NCI)
Nicholas P Restifo (NCI)


Patent Status:
HHS, Reference No. E-069-2010/0
US, Application No. 61/420,825 filed 08 Dec 2010


Relevant Publication:
  1. Palmer DC and Restifo NP. [ PMID 19879803 ]



For Licensing Information Please Contact:
Samuel Bish Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: bishse@mail.nih.gov
Phone: 301-435-5282
Fax: 301-402-0220


Ref No: 2301

Updated: 08/2011

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