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Methods of Producing Effective T-cell Populations Using Akt Inhibitors

19:00 EST 12 Nov 2017 | NIH

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.

IC: 
NCI
NIH Ref. No.: 
E-013-2016/0
Advantages: 
  • No other pharmacologic approach available to effectively uncouple T-cell expansion and differentiation
  • Produces increased number of persistent, cancer reactive T-cells
Applications: 
  • 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-cells
Provider Technology ID: 
3203
Updated On: 
Nov 13, 2017
Date Published: 
Monday, November 13, 2017
Provider Classifications: 
Publications: 
Patent Application: 
62/243,834
PCT/US2016/057307
Patent Authority: 
US
PCT
Licensing Contacts: 
Lead Inventor: 
Inventor IC: 
NCI
NCI
Inventor Lab URL: 
http://irp.nih.gov/pi/nicholas-restifo
LPM FIrst Name: 
Andrew
LPM Last Name: 
Burke
LPM Address: 
9609 Medical Center Drive, Room 1E-530 (MSC 9702)
LPM City: 
Rockville
LPM Zip: 
20850-9702
Inv Is lead: 
LPM State: 
MD
LPM Phone: 
240-276-5484
LPM Suffix: 
Ph.D.
LPM Organization: 
NIH Office of Technology Transfer
LPM Fax: 
240-276-5504
DTDT Classification: 
Cancer
Therapeutics
Research Materials
Cancer
Research Tool
Therapeutic (small molecule)
DTDT Description: 
Cancer
Cancer - Therapeutics
Cancer - Research Materials
Cancer
Research Tool
Therapeutic (small molecule)
Pat Filing Date: 
2015-10-20
2016-10-17
Publication Link: 
https://www.ncbi.nlm.nih.gov/pubmed/25432172
https://www.ncbi.nlm.nih.gov/pubmed/25336630
Publication Caption: 
PMID 25432172
PMID 25336630
Publication Title: 

Crompton JG, et al.

van der Waart AB, et al.

Disease Area Term: 
Collaboration Sought: 
Yes
Institute or Center: 
Collaboration Opportunity: 

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.

Related Patent Publish Date: 
1490677200
1412226000
1490677200
1412226000
Related Patent Application: 

15/514,942

PCT/US2014/058796

15/515,055

PCT/US2014/058805

Related Patent Authority: 
US
PCT
US
PCT
Related Invention: 
E-229-2014/0
E-233-2014/0
E Number Only: 
E-013-2016
Inventor First Name: 
Nicholas
Joseph
Inventor Last Name: 
Restifo
Crompton

Original Article: Methods of Producing Effective T-cell Populations Using Akt Inhibitors

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