Inhibition of T Cell Differentiation and Senescence by Overexpression of Transcription Factor c-Myb


Adoptive Cell Therapy (ACT) is a promising technique that uses a patient's own T cells to treat cancer. The process requires removing and engineering a patient's T cells to express a chimeric antigen receptor (CAR) or T cell receptor (TCR) that targets a specific cancer antigen. When the modified T cells are reintroduced into the patient, the T cells attack and kill cancer cells that express the antigen, thereby treating the patient. Although ACT holds a great deal of promise, there are still technical drawbacks to be overcome, such as loss of anti-tumor activity due to T cell senescence.

This invention addresses this technical drawback by using T cells that express the transcription factor c-Myb (or a functional variant thereof) at elevated levels as the host for transduction with CARs or TCRs. T cells that exhibit elevated expression of c-Myb display inhibited differentiation, allowing the cells to survive, proliferate and serve in a therapeutic capacity for a longer duration. Since it is believed that these characteristics can increase the effectiveness of ACT, T cells with elevated levels of c-Myb expression are strong candidates for use in ACT.



Potential Commercial Applications: Competitive Advantages:
  • Adoptive Cell Therapy (ACT) using chimeric antigen receptors (CARs), or engineered T cell receptors (TCRs)
  • Treatment of cancers that express specific cell surface proteins
 
  • Elevated expression of c-Myb in T cells allows them to resist differentiation, thus cells survive and proliferate in greater numbers
  • Increased survival and proliferation of T cells allows for a prolonged therapeutic effect


Development Stage:
Pre-clinical (in vivo)

Inventors:

Luca Gattinoni (NCI)  ➽ more inventions...

Yun Ji (NCI)  ➽ more inventions...

Sanjivan Gautam (NCI)  ➽ more inventions...


Intellectual Property:
Application No. PCT/US2016/048435
Application No. 62/209,497

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-232-2015
Updated: May 16, 2018