With their low toxicities, immune therapies seem tailor-made for pediatric cancer patients where long-term effects caused by conventional therapies are of great concern. Childhood cancer patients can suffer the consequences of chemotherapy throughout their lifetime, including fertility issues, cardiac toxicities, learning impairment and more. In fact, many cancer immunology experts believe immune therapies may be a paradigm changer, eventually replacing chemotherapy as the first-line treatment in many pediatric cancers because of its ability to spare patients from these dangerous toxicities.
Take, for example, Hodgkin’s lymphoma. It is a common childhood cancer that responds well to chemotherapy, but treatment is long and toxic, and the growing brains and bodies of children and adolescents are particularly susceptible to the damaging effects of chemotherapy. New research shows Hodgkin’s lymphoma may be one of the best responders so far to anti-PD-1 immune checkpoint blockade therapy, with response rates approaching 90 percent. There have been excellent responses and low toxicities even in patients whose cancer resisted standard drug treatment.
Researchers like pediatric oncologists and cancer immunology experts Brian Ladle and Christopher Gamper say there is emerging evidence that immune therapies may be more effective against chemotherapy-resistant cancer. They offer new hope for pediatric patients with cancers that currently cannot be cured with standard treatments.
Ladle is excited about this less toxic approach to destroying cancers. “It’s a privilege to be able to cure kids of cancer, but right now, what we have to put them through to get them there is unacceptable,” he says. “We have to do better for them.”
While he doesn’t think immune therapy will completely replace the need for surgery and chemotherapy, he believes it has great potential to reduce the amount and duration of treatment. More importantly, since immune cells can travel anywhere throughout the body—inside bones and to organs and tissues—they have a unique ability to find and destroy lingering cancer cells that often result in the recurrence and spread of cancers.
Ladle and Gamper are discovering crucial links between T cell behavior, the main cells activated in an immune response, and the epigenetic or chemical environment of T cell DNA. Although the DNA code of a T cell that has never been activated is identical to that of T cells engaged in an immune attack, significant changes occur in the chemicals that surround the DNA that help signal it to remain dormant or go into action. As a result, Ladle and Gamper are deciphering the normal epigenetic activity of immune T cells and exploring whether existing epigenetic-targeted treatments might be able to improve immune responses to cancer.
Ladle and Gamper believe epigenetic drugs may augment the effectiveness of other immune treatments, such as cancer vaccines and immune checkpoint blockers. They are also looking for other proteins expressed by tumor cells that work like PD-1 to shut down an immune response to cancer. In addition, new pediatric oncology physician-scientist Nico Llosa is working on ways to use PD-1 blockade and other similar immune agents to fight pediatric cancers.
While there have been significant advances in cancer immune therapies in adults over the last few years, translating these findings to pediatric cancers lags far behind. “This is the main reason I wanted to work in pediatric oncology,” says Ladle. “There is so much promise. We know that children’s immune systems are much more responsive than adults’.” What Ladle envisions are treatments that harness and deploy the body’s own natural ability to fight cancer and decrease the need for invasive surgeries and toxic, cell-poisoning drugs.