A new study has revealed the mechanism that causes heart-related side effects of one of the best groups of cancer drugs, the discovery of which has led to a significant improvement in cancer treatment. This discovery will help develop solutions to this problem in the future, making these effective drugs safer.
Effective medicine
The immune system protects the body from invaders—such as germs—and cellular changes that might be harmful. The immune system has its own checks and balances to keep it from being overly aggressive or from destroying healthy and harmful cells indiscriminately.
The proteins on the surface of T cells are part of the checks and balances that govern the immune system. T cells scour the body for foreign cells using proteins called receptors on their surfaces to exchange signals with other cells. During this exchange of signals, called a checkpoint, if the T cell decides that a cell is normal or healthy, it moves on to examine other cells, as explained by the website of the City of Hope Cancer Hospital in the United States of America.
Sometimes the immune system doesn’t know that cancer cells are foreign. They are actually the body’s own cells, but for some reason they have become out of control. Cancer cells may send deceptive signals at checkpoints that tell T cells that they are not harmful.
Checkpoint inhibitors work by blocking receptors that cancer cells use to send signals that trick T cells into thinking they are healthy cells. When the signal is blocked, T cells may be better able to distinguish between a cancer cell and a healthy cell and launch an attack. Cytotoxic T-cell antigen 4 is a type of protein found on T cells.
Cytotoxic T-lymphocyte antigen 4 was the first immune checkpoint protein to be targeted by immunotherapy. These drugs prevent T cells from binding to proteins that stop them from working.
Inhibiting T-cell antigens with these drugs is an effective treatment for some types of cancer, but it can damage the heart.
New discovery
Experiments in mice showed that blocking CTCA4 activates a type of T cell called T17, which in turn triggers a series of processes that ultimately lead to increased inflammation. Blocking this activation stopped the damage to the heart.
New research, published in the Journal of the Federation of American Societies for Experimental Biology on August 7, has revealed the mechanisms involved in this side effect, a discovery that could be used to help prevent heart damage.
Experience
Heart enlargement and heart failure were induced in lab mice. Two weeks later, the mice received two weekly injections of the checkpoint inhibitor drug. Giving the drug worsened the deterioration in heart function. Further experiments revealed that the drug also significantly increased levels of inflammatory factors.
“Targeting this axis could provide preventive or therapeutic strategies for managing cardiotoxicity in patients undergoing anti-CTCA4 immune checkpoint inhibitor therapy,” the authors wrote, according to EurekAlert.