Methods of Producing Effective T-cell Populations Using Akt Inhibitors


Adoptive cell therapy (ACT) uses cancer reactive T-cells to effectively treat patients. However, several obstacles inhibit the successful use of ACT for cancer treatment.  Current approaches for the expansion of T-cells may produce T-cells with a terminally differentiated phenotype that is associated with diminished anti-tumor activity and poor capacity for long-term persistence. Thus, there is a need for improved methods of obtaining an isolated population of effective T-cells for ACT. 

Researchers at the NCI have developed a method of producing large populations of minimally-differentiated T-cells using an Akt inhibitor. The researchers discovered that inhibition of the serine/threonine kinase, Akt, also known as protein kinase B, effectively uncouples T-cell expansion from differentiation. This uncoupling allows for the generation of more robust T-cells with greater anti-tumor efficacy than differentiated T-cells. The researchers found that Akt inhibition also promotes the genetic and metabolic characteristics of long-lived memory T-cells. This discovery provides a method of producing an isolated population of cancer reactive T-cells suitable for ACT.

The National Cancer Institute, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize a novel method of producing effective T-cell populations using Akt inhibitors.



Potential Commercial Applications: Competitive Advantages:
  • Clinically-feasible method of using small molecules to enhance the efficacy of immunotherapy for advanced cancer patients
  • Useful for the generation of highly effective cancer reactive T-cell
 
  • No other pharmacologic approach available to effectively uncouple T-cell expansion and differentiation
  • Produces increased number of persistent, cancer reactive T-cell


Development Stage:
Pre-clinical (in vivo)

Related Invention(s):
E-229-2014
E-233-2014


Inventors:

Nicholas Restifo (NCI)  ➽ more inventions...

Joseph Crompton (NCI)  ➽ more inventions...


Intellectual Property:
Application No. 62/243,834
Application No. PCT/US2016/057307

Publications:
Crompton JG, et al. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. PMID 25432172
van der Waart AB, et al. Inhibition of Akt signaling promotes the generation of superior tumor-reactive T-cells for adoptive immunotherapy. PMID 25336630

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-013-2016
Updated: Dec 5, 2017