Treatments that unleash the body’s own disease-fighting cells against cancer – an approach known as immunotherapy – have been heralded as the “Breakthrough of the Year” by Science magazine.
The accolade reflects the remarkable success of techniques that allow immune system T cells to make a sustained assault on cancer cells. In early-stage clinical trials, these techniques have spurred long-lasting remissions in some patients with advanced cancers.
One such technique – which uses an antibody to release the brakes on a T cell attack on cancer cells – has a long pedigree at Dana-Farber. In the early 2000s, Dana-Farber scientists led by Gordon Freeman, PhD, were the first to describe how molecules on cancer cells and T cells interact to turn off a T cell attack. This discovery opened the way to drug agents that, by blocking that interaction, allow T cells to mount their assault.
The mechanism discovered by Freeman and his colleagues involves a protein called PD-L1, which sways from the surface of a few specialized normal cells, and a complementary protein on T cells called PD-1. When PD-L1 latches onto PD-1, the T cell leaves the normal cell alone.
Freeman’s team later found that cancer cells often cloak themselves in PD-L1 (and a related protein, PD-L2) as well – thereby avoiding an immune system attack.
Pharmaceutical companies quickly seized on the finding, developing antibodies that can block PD-1, PD-L1, or PD-L2. Although the clinical trials of these drugs are still in their early stages, the results are highly promising.
One trial for example, tested a PD-1 and a PD-L1 blocker in hundreds of patients with advanced cancers that were no longer being controlled by other therapies. In all, 18 percent of patients with non-small cell lung cancer had their tumors shrink partially or completely, as did 28 percent of patients with melanoma, and 27 percent of those with kidney cancer. The hallmark of many of these remissions was their persistence: two-thirds of the patients who benefited from the drugs were still in remission when investigators checked them a year after treatment. Several other drugs that work by a similar mechanism are currently being tested, with results looking equally promising.