AUSTIN (KXAN) – University of Texas researchers led a team that found a drug that restores effectiveness of immune cells in fighting cancer, the university announced Monday.
According to the announcement, the drug, called PEG-MTAP, slows the growth of tumors, extends lifespan and boosts the efficacy of immunotherapy in mice with melanoma, bladder cancer, leukemia and colon cancer.
DNA deletion and cancer
Many cancers delete a stretch of DNA called 9p21. That deletion occurs in 25%-50% of certain cancers such as melanoma, bladder cancer, mesothelioma and some brain cancers, UT said.
According to the announcement, cancers with the 9p21 deletion mean worse outcomes for patients and resistance to immunotherapies.
The 9p21 deletion leads to the loss of genes that produce cell cycle regulators or proteins that keep healthy cells growing and dividing at a slow, steady rate, UT said. So when those genes are lost, cells can grow unchecked and that is what makes them cancerous.
The 9p21 deletion helps cancer cells avoid getting taken out by the immune system, in part by prompting the cancer to pump out a toxic compound called MTA, according to the announcement. That compound impairs normal functioning of immune cells and also blocks the effectiveness of immunotherapies.
Also deleted is a housekeeping gene that produces an enzyme that breaks down the toxin MTA, UT said. It’s this loss, according to lead researcher Everett Stone, that allows cancer cells to deactivate the immune system.
What the drug does
“In animal models, our drug lowers MTA back down to normal, and the immune system comes back on,” Stone, a research associate professor in the Department of Molecular Biosciences and associate professor of oncology at Dell Medical School, said.
“We see a lot more T cells around the tumor, and they’re in attack mode.” Stone said. “T cells are an important immune cell type, like a SWAT team that can recognize tumor cells and pump them full of enzymes that chew up the tumor from the inside out.”
He said he envisioned the drug being used in combination with immunotherapies to boost their effectiveness.
The researchers plan to do more safety tests on their drug and are seeking funding to take it into human clinical trials.
The research is published in the journal Cancer Cell.