Exposing T cells to Fas Ligand (FasL)-Fas Receptor (FasR) Antagonists Withholds Differentiation and Increases Expansion Making T cells More Suitable for Use in Cancer Immunotherapy

NIH scientists have developed methods to make a better immunotherapy by exposing T cells to Fas ligand (FasL) or Fas receptor (FasR) antagonists and agonists. Researchers have found that FasL-FasR antagonists suppress T cell differentiation leaving them in a naïve state. These T cells are a more ideal cell type for adoptive cell transfer therapies since they have not exhausted their effector functions and demonstrate greater proliferation, enhanced persistence and survival, and better activity against their target antigen when infused in vivo to treat cancer. Also, the prevention of T cell differentiation/effector function in vivo has implications for autoimmune diseases and syndromes. FasL-FasR agonists enhance T cell differentiation towards more effector-like cells. Enhancing the differentiation of T cells is expected to be useful in treating cell proliferation disorders, such as leukemias, lymphomas, or Wiskott-Aldrich syndrome.


FasL (or cluster of differentiation 95L) is a transmembrane protein in the tumor necrosis factor (TNF) family. FasR (or apoptosis antigen 1, CD95, or TNF receptor superfamily member 6) is a transmembrane protein belonging to the TNF receptor/nerve growth factor receptor superfamily. Normally, when FasL binds to FasR, a cell death signal is triggered in the cell. Antagonists of FasL-FasR interaction may include caspase inhibitors, mutated FasL/FasR, RNAi, or FasL/FasR antibodies. Agonists may include FasL/FasR encoding nucleotides. CRADA Opportunity: The Surgery Branch of the NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the prevention of T cell differentiation and effector function as part of Immunotherapy. For collaboration opportunities, please contact Steven A. Rosenberg, M.D., Ph.D. at sar@nih.gov. Click here to view the NCI collaborative opportunity announcement.

Source: http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2456

Jennifer Garner Jennifer Gimenez Jennifer Love Hewitt Jennifer Morrison Jennifer ODell