Immunotherapies are in the forefront for treating autoimmune diseases and cancer. Northwestern University and the University of California San Francisco conducted a study using genes that have the potential of being “on/off” switches to fight two categories of diseases.
The study was published in Nature’s April 2020 journal. The article describes regulatory T cells commonly known as Tregs, together with genes that scientists have identified as having the potential to clinically manipulate Tregs to fight disease.
Boosting or Suppressing the Immune system
Tregs are a type of white blood cell (leukocyte) that is critical to the immune system. Tregs ward off autoimmune disease by preventing the body from turning against itself.
The scientists had been previously aware of their role in keeping the body in proper working order. They now have discovered that it is possible to manipulate Tregs in two different directions to fight cancer and autoimmune disease.
With just a small change in the gene, the “switch” can cause Tregs to stand back and permit the immune system to attack the cancer cells.
The opposite is true when another gene that guards the immune system is changed. The immune system is then prevented from damaging the body’s tissues as in autoimmune diseases.
Tregs and Effector T Cells
Tregs are responsible for lessening damage by another cell called effector T cells. These cells target foreign invaders and act against tumors.
After the effector T cells have competed their mission, the Tregs take over and assist the immune system in returning to its normal state.
Scientists have discovered that if Tregs are weakened and are unable to restrain the effector T cells, autoimmune disease will develop. The effector T cells will attack the body’s tissues if not restrained.
The reverse is true when there are high levels of the suppressing Tregs in an area around a tumor. This precludes the immune system from destroying the tumor.
The scientists were able to flip a switch to lessen the suppression. The result was an anti-tumor immune response.
And the Winners Are . . .
Co-author of the study, Dr. Alexander Marson, said that the study could assist in boosting immune response to cancer therapy or conversely it could assist in suppressing it with respect to autoimmune diseases.
With the use of CRISPR gene targeting technology, a protein called ubiquitin specific peptidase 22 (Usp22) emerged out of 489 regulatory proteins that exist in Tregs or T effector cells.
Usp22 reduces Treg cells’ ability to suppress the immune system and leads to autoimmune disease.
The other side of the coin is that Usp22 inhibits the growth of lymphoma and other tumors.
Again, using the same screening technology, another regulatory protein emerged called ring finger protein 20 (Rnf20) that had the opposite effect of Usp22.
Stabilizing Treg Function
Co-author Dr. Jeff Bluestone commented that one of the key issues involving cell therapy for treatment of organ transplantation, degenerative diseases, and autoimmune diseases is knowing how to stabilize Treg function.
Dr. Bluestone is CEO of Sonoma Biotherapeutics that is focused on developing cell therapies for autoimmune diseases.
Dr. Cortez joins Dr. Bluestone in expressing their enthusiasm in the CRISPR screening that is fine-tuning Treg function for the treatment of cancer and autoimmune diseases. They agreed that Rnf20 and Usp22 are powerful targets in Treg immunotherapies.