Cancer Drug Restores Immune System's Ability to Fight Tumors
Published:31 Oct.2023 Source:University of Texas at Austin
A new, bio-inspired drug restores the effectiveness of immune cells in fighting cancer, a team led by researchers at The University of Texas at Austin has found. In mouse models of melanoma, bladder cancer, leukemia and colon cancer, the drug slows the growth of tumors, extends lifespan and boosts the efficacy of immunotherapy.
Many cancers delete a stretch of DNA called 9p21. The deletion helps cancer cells avoid getting detected and wiped out by the immune system, in part by prompting the cancer to pump out a toxic compound called MTA that impairs normal functioning of immune cells and also blocks the effectiveness of immunotherapies. Stone envisions the drug being used in combination with immunotherapies to boost their effectiveness. The 9p21 deletion leads to the loss of some key genes in cancer cells. Gone are a pair of genes that produce cell cycle regulators -- proteins that keep healthy cells growing and dividing at a slow, steady rate. When those genes are lost, cells can grow unchecked. That's what makes them cancerous. Also deleted is a housekeeping gene that produces an enzyme that breaks down the toxin MTA. It's this loss, according to Stone, that lets cancer cells acquire a new superpower: the ability to deactivate the immune system.
To create their drug candidate, Stone and his colleagues started with the helpful enzyme that's naturally produced by the body to break down MTA and then added flexible polymers. The researchers plan to do more safety tests on their drug, called PEG-MTAP, and are seeking funding to take it into human clinical trials.