Improved TSCM Stem Cells May Beat Cancer

American researchers from the Georgetown Lombardi Comprehensive Cancer Center have been able to reprogram T lymphocytes into memory T stem cells (TSCM) – long-lived “super immune cells” with high anti-tumor activity.

To reprogram cells, a new method developed by the authors was used that suppresses the activity of the MEK1 and MEK2 proteins. Several MEK inhibitors are currently used to effectively treat melanoma, but this study demonstrates that these inhibitors not only target certain types of cancer cells but more generally reprogram T cells to fight many types of cancer.

“Although immunotherapies have improved survival for cancer patients over recent years, survival rates remain suboptimal. Therefore, there is an urgent need to develop novel, more effective anti-cancer immunotherapies”, – says Samir N. Khleif, MD, the leader of the group that made the discovery, published in the journal Nature Immunology. “Our research shows that using drugs that have already been approved for human use may significantly enhance currently available immune therapeutic approaches, thereby leading to better and more durable anti-cancer responses.”

The researchers conducted laboratory experiments with human cells and then confirmed the effectiveness of such an approach in mice. Scientists were able not only to identify a new strategy for reprogramming T cells into memory stem T cells by inhibiting MEK1/2 but also to identify a new molecular mechanism by which TSCMs were induced.

The team found that the new reprogramming technique could significantly improve T-cell therapy for cancer patients. Currently, CAR T cell therapy is widely used in certain types of cancer and in clinical trials. This method involves the introduction of the patient’s own T lymphocytes with an attached chimeric receptor programmed to recognize the target of tumor cells.

In the new experiment, human T cells were reprogrammed with MEK inhibitors in TSCMs. In addition, when treating mice with MAO inhibitors, it was also found that reprogramming T cells induce effective TSCMs.

Stem cell research has played a vital role in this century in enhancing the progress against many diseases. Recent public and private support for stem cell therapy is very gratifying”, – says Khleif. “Having stem cell research-specific funding from both governmental and private funders will greatly help accelerate the development of this under-utilized area of research.”

After demonstrating that MEK inhibitors enhance anti-tumor immune responses, the researchers are planning clinical trials to test their research method in cancer patients.

“Our approach is completely innovative, and we really want it to be applied in clinical practice as soon as possible”, – concludes Hleif.