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.

Competitive Advantages:

• 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

Commercial Applications:

• Adoptive Cell Therapy (ACT) using chimeric antigen receptors (CARs), or engineered T cell receptors (TCRs)
• Treatment of cancers that express specific cell surface proteins