Changing the way regulatory T cells fight tumors

INDIANAPOLIS — New research by the IU School of Medicine is looking at new ways to fight aggressive cancers. Right now the focus is on enhancing treatment options for aggressive cancers like triple negative breast cancer.

“We have pretty high confidence that this will be a novel therapy for breast cancer as well as for other cancers too,” said Dr. Baohua Zhou, the co-responding author of the study with the IU School of Medicine.

It all has to do with studying the behavior of immunosuppressive cells also known as regulatory T cells in tumors turning them from tumor protectors into tumor fighters. 

For some background, regulatory T cells are known to keep our immune systems in check protecting us from getting sick, so getting rid of these cells completely would not be good for our bodies. However, within the tumor, these cells can block the immune system from detecting and attacking cancer cells, which can lead to a number of problems. But, with this new research, scientists are reprogramming how these cells work, so that they can fight against tumors instead of protecting them.

“Our key point here is to try to maintain a majority of the function of this group of cells to not cause autoimmune disease but can still enhance the anti-tumor immune response,” Dr. Zhou said.

To do this, the researchers are specifically looking at a gene called FOXP3 which controls the development and function of regulatory T cells. Our bodies produce two versions of the FOXP3 protein, a full-length version and a short version. A patent pending drug known as Morpholino is targeting FOXP3 forcing the regulatory T cells to predominantly produce the short version. In turn, this helps reprogram the tumor-protective regulatory T cells into helper-like cells that help other immune cells to destroy the tumor from the inside.

“This itself opened a new avenue towards cancer immunotherapy,” said Dr. Naresh Singh, the co-first author of the study with the IU School of Medicine. “I think it will really help the cancer patients and also increase the outcomes of the new immunotherapies.”

So far, the trials have only been done in mice but they’ve proven to be very successful over the last few years.

“In those mice, we have really seen some tremendous results with this drug and I think we are very hopeful that within the clinical trials also we will have some really good outcomes,” Dr. Singh said.

There is still a long way to go before this can become a standard treatment but clinical trials are the next step to make this a reality.

There will be more research going forward to use these methods to treat other cancer types too like colorectal cancer and melanoma.