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.
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
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.
In vitro data available
In vivo data available (animal)
Inventors: Douglas C Palmer (NCI) Nicholas P Restifo (NCI)
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: firstname.lastname@example.org Phone: 301-435-5282 Fax: 301-402-0220