by Rafaela Prifti/
Nature, a world’s leading multidisciplinary science journal, published a study on immunotherapy treatment that stemmed from a failed clinical trial. It led to an important finding in treatment strategy.
Although immunotherapy is only available to a few types of cancer, it has seen advances that have helped patients with metastatic and spreading disease that have pushed the boundaries of treatment therapies. Immunotherapy works by harnessing the power of your body’s own immune system. Yet, it has had limited success. Only around 20 percent of patients who receive it get the benefit of a long term remission. This week’s Nature article provides critical clues to why many immunotherapies trigger dangerous side effects—and point to a more effective strategy for treating patients with solid tumors.
Cancer patients in the UK were reporting negative side effects during a cancer immunotherapy trial. It prompted researchers at La Jolla Institute for Immunology Center for Cancer Immunotherapy and University of Liverpool to reexamine the data, and patient samples.
While around 20 to 30 percent of solid cancer patients got long-term remission, some people saw no change after immunotherapy, and others develop serious problems in their lungs, bowel, and even skin during treatment. These side effects can be debilitating, even fatal, and these patients are forced to stop receiving the immunotherapy.
The researchers at La Jolla Institute and the University of Liverpool worked with samples from a recent clinical trial in the UK for patients with head and neck cancers. “The patients were given an oral cancer immunotherapy called a PI3Kd inhibitor. At the time, PI3Kd inhibitors had proven effective for B cell lymphomas but had not yet been tested in solid tumors,” the study says.
PI3Kd inhibitors work by inhibiting “regulatory” T cells called Tregs inside tumors to allow other T cells – effector T cells – to generate cancer-killing CD8+ T cells. The article cites that 12 of the 21 patients in the trial had to discontinue treatment early because they developed inflammation in the colon, a condition called colitis. The team went back to the data and samples to see how the drug was affecting the immune cells. Using a method known as the single-cell genomic sequencing, it was revealed that in the process of increasing tumor-fighting T cells in tumors, the inhibitor, also blocked a specific Treg cell subset from protecting the colon, leaving it exposed to pathogenic cells.
It was determined that the cancer trial patients had been given a larger inhibitor dose than they needed, which has disrupted the delicate balance of the immune cells in the gut.
The new study shows the importance of studying not just personalized therapies but personalized therapy doses and specific sequence, which will be applied in the next clinical human trial. The team of researchers found that intermittent dosing could be a valid treatment strategy that combines sustained anti-tumor immunity with reduced toxicity.
Photo Credit Nature