Methods for Producing Stem Cell-like Memory T cells for Use in T cell-based Immunotherapies


T cells currently employed for T cell-based immunotherapies are often senescent, terminally differentiated cells with poor proliferate and survival capacity. Recently, however, NIH scientists identified and characterized a new human memory T cell population with stem cell-like properties. Since these T cells have limited quantities in vivo, the scientists have developed methods by which high numbers of these cells can be generated ex vivo for use in T cell-based immunotherapies. Specifically, this technology describes a method for generating the stem cell-like memory T cells by stimulating naive T cells in the presence of inhibitors of GSK-3beta. It also describes a method for obtaining the stem cell-like memory T cells by sorting T cell lymphocytes using flow cytometry. These stem cell-like memory T cells display enhanced proliferation and survival upon transfer, have the multipotent capacity to generate all memory and effector T cell subsets and show increased anti-tumor activity in a humanized mouse tumor model. Consequently, the coupling of T cell receptor or chimeric receptor gene transfer with this method will enable the generation of a large number of memory stem cells with the desired specificity to effectively treat patients with cancer and chronic infectious diseases.

Potential Commercial Applications: Competitive Advantages:
  • Ex vivo generation of stem cell-like memory T cells for T cell-based immunotherapy
  • Treatment for patients with cancer and chronic infectious diseases
 
  • Enhanced proliferation and survival upon transfer
  • Multipotent capacity to generate all memory and effector T cell subsets
  • Increased anti-tumor activity


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


Inventors:

Luca Gattinoni (NCI)  ➽ more inventions...

Nicholas Restifo (NCI)  ➽ more inventions...


Intellectual Property:
PCT Application No. PCT/US2012/053947
US Application No. 14/425,713
US Application No. 16/410,327

Publications:
Gattinoni L, et al. PMID 21926977
Gattinoni L, et al. PMID 19525962
Lugli E, et al. PMID 23222456

Collaboration Opportunity:

The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the use of T memory stem cells for T cell-based immunotherapies. For collaboration opportunities, please contact Luca Gattinoni at gattinol@mail.nih.gov or 301-451-6914, or Nicholas Restifo at restifo@nih.gov or 301-496-4904.


Licensing Contact:
Abritee Dhal,
Email: abritee.dhal@nih.gov
Phone: 240-276-5530

OTT Reference No: E-174-2012-0
Updated: Oct 13, 2015