Reprogramming of T cells into highly active “superimmune cells” can enhance the benefits of immunotherapy

Reviewed by Emily Henderson, B.Sc.November 23, 2020

According to new research from the Georgetown Lombardi Comprehensive Cancer Center, T cells of the immune system have been reprogrammed into regenerative stem cell-like memory (TSCM) cells which are highly active and long-lasting “super immune cells” with strong anti-tumor activity. .

Reprogramming involves a new approach developed by researchers that inhibits the activity of proteins known as MEK1 / 2. Currently, several MEK inhibitors are used to effectively treat melanoma, but this study shows that MEK inhibitors do not take. it only targets certain types of cancer cells, but rather, more generally, they reprogram T cells to fight many types of cancer.

The discovery appears on November 23, 2020, in Nature Immunology.

“Although immunotherapies have improved the survival of cancer patients in recent years, survival rates remain sub-optimal. Therefore, there is an urgent need to develop new, more effective anti-cancer immunotherapies,” says Samir N. Khleif, MD. , director of The Jeannie and Tony Loop Immuno-Oncology Laboratory and head of the team that conducted this research. “Our research shows that the use of drugs that are already approved for human use, can significantly improve immune therapeutic approaches currently available, thus leading to anti-cancer responses better and more durable.”

The researchers performed experiments with human cells in the laboratory and then confirmed the effects of such an approach on mice. The researchers were not only able to identify a new strategy for reprogramming T cells into TSCM cells using MEK1 / 2 inhibition, but they were also able to identify a new molecular mechanism by which TSCMs were induced.

Scientists have found that reprogramming of T cells into TSCM can significantly improve T cell therapies for cancer patients. T cell therapy is a process widely used in specific tumors and clinical trials, in which T cells of the immune system are separated from a patient’s blood, engineered and expanded with special tumor targeting capabilities and reinfused into the patient to fight the cancer . In their experiments, human T cells were reprogrammed with MEK inhibitors in TSCM; Furthermore, when treating mice with MEK inhibitors, reprogramming of T cells was also found to induce effective TSCM.

Stem cell research has played a pivotal role this century in improving progress against many diseases. Recent public and private support for stem cell therapy is very gratifying. Having specific funding for stem cell research from government and private funders will greatly help accelerate the development of this underutilized area of ​​research. “

Samir N. Khleif, MD, Director of the Jeannie and Tony Loop Immuno-Oncology Laboratory

Now that MEK inhibitors have been shown to enhance an antitumor immune response, researchers are starting to look into clinical trial design to test their research approach in cancer patients. “Our approach is quite new and we look forward to seeing it put into practice in the clinical setting as soon as possible,” Khleif concludes.