Compound puts pancreatic cancer in immunotherapy's sights
Immunotherapy is a form of cancer treatment that seeks to supercharge the body's natural immune defenses, and it's become a viable therapy for certain types of the disease. Pancreatic cancer is one that has so far been able to evade its advances, but scientists are now reporting a discovery that might help the immune system regain the upper hand.
Around 57,000 people in the US will be diagnosed with pancreatic cancer in 2019 according to the American Cancer Society, of which 46,000 will die from the disease. Traditional treatments like chemotherapy and radiation therapy aren't as effective as they are against other cancers, making for a five-year survival rate of around just eight percent.
Immunotherapy doesn't work very well against pancreatic cancer, either, and at least part of the reason for this are what are known as myeloid cells. These are versatile types of immune cells that live in and around tumors and either recruit killer T cells to attack them, or suppress the activity of the T cells and instruct them to ignore the tumor instead. Unfortunately, when it comes to pancreatic cancer, they tend to do the latter.
In this way, myeloid cells are a double-edged sword when it comes to pancreatic cancer, and medical scientists at Washington University in St Louis have been investigating how they might get it swinging in more favorable ways. This led them to a chemical compound called ADH-503, which they found could change the migration patterns of myeloid cells, and populate the tumor with versions that promoted rather than dampened the immune response.
They then combined this with a common immunotherapy drug known as a PD-1 checkpoint inhibitor, which works by releasing a brake that naturally prevents T cells from attacking cancer cells. On their own these drugs had no effect in mice with pancreatic cancer, but when paired with ADH-503 the scientists began to see some results.
In mice treated with the combination of drugs, their tumors shrank and the animals survived for far longer. In some cases, the tumors disappeared entirely within a month and the mice went on to live for at least four months (the researchers didn't monitor them beyond that point). Mice that went untreated in the experiments died within six weeks.
"Pancreatic cancer is a highly lethal disease, and we are in desperate need of new therapeutic approaches," says co-senior author David DeNardo, PhD, an associate professor of medicine and of pathology and immunology at Washington University School of Medicine. "In animal studies, this small molecule led to very marked improvements and was even curative in some cases. We are hopeful that this approach could help pancreatic cancer patients."
The scientists note the uncertainty in translating results of this kind from mice to humans, but are optimistic about the possibilities their discovery opens up. They will conduct further studies to see if the compound is safe and effective in people, with phase one safety trials planned for later in the year.
The research was published in the journal Science Translational Medicine.