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 proliferative and survival capacity. Recently, however, scientists at the National Cancer Institute (NCI) 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 invention describes a method for generating the stem cell-like memory T cells by stimulating naive T cells in the presence of GSK-3beta inhibitors. The invention also provides methodology 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 vivo)

Inventors:

Luca Gattinoni (NCI)  ➽ more inventions...

Nicholas Restifo (NCI)  ➽ more inventions...


Intellectual Property:
Application No. PCT/US2012/053947
Application No. 14/425,713

Publications:
Gattinoni L, et al., A human memory T cell subset with stem cell-like properties.  PMID 21926977
Gattinoni L, et al., Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells.  PMID 19525962
Lugli E, et al., Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cells.  PMID 23222456

Collaboration Opportunity:

Licensing and research collaboration


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-174-2012
Updated: Aug 15, 2018