While acknowledging that the full potential of cancer immunotherapy remains unclear, the editors of the journal Science said that the approach of using the immune system to attack tumors marks a turning point in the treatment of cancer.1 The successes of cancer immunotherapy in clinical trials in 2013, which were decades in the making, displayed such promise as a treatment strategy, it rose to the top of the journal’s list of the year’s 10 most important scientific breakthroughs.
Other scientific achievements singled out by Science include breakthroughs in solar cell technologies, genome-editing techniques, and vaccine design strategies.
“This year there was no mistaking the immense promise of cancer immunotherapy,” Tim Appenzeller, Science’s News Editor, said in a statement. “So far, this strategy of harnessing the immune system to attack tumors works only for some cancers and a few patients, so it’s important not to overstate the immediate benefits. But many cancer specialists are convinced that they are seeing the birth of an important new paradigm for cancer treatment.”
Early Pioneers
Science credited many of today’s advances in cancer immunotherapy to the early work of French researchers in the late 1980s. Their identification of a new protein receptor on the surface of T cells, called cytotoxic T-lymphocyte antigen 4 (CTLA-4), led to the discovery by cancer immunologist James Allison, PhD, Chair of Immunology at The University of Texas MD Anderson Cancer Center and Executive Director of its Moon Shots Program immunotherapy platform, that CTLA-4 prevented T cells from launching full-force immune attacks. Nearly a decade later, in 1996, Dr. Allison showed that blocking CTLA-4 in mice could unleash T cells against their tumor cells, shrinking them dramatically.
Steady Progress
A few years earlier, a Japanese biologist discovered that a molecule expressed in dying T cells, which he called programmed death 1 (PD-1), also put the brake on T cells. The first clinical trial of an anti–PD-1 antibody began in 2006 in 39 patients and five different cancers. Two years later, five of the participants, all with refractory disease, saw their tumors shrink.
Then in 2010, Steven Rosenberg, MD, PhD, of the Surgery Branch in the National Cancer Institute’s Center for Cancer Research, published encouraging results from his study of chimeric antigen receptor (CAR) therapy, in which a patient’s T cells are genetically engineered to attack tumor cells. And research led by Carl June, MD, Director of Translational Research at the Abramson Cancer Center at the University of Pennsylvania, of a type of CAR cell called CTL019 in patients with leukemia has shown durable remissions in some patients.
The result from the success of clinical studies of immunotherapy is encouraging pharmaceutical companies to develop antibodies, such as anti–PD-1. And in 2011, the U.S. Food and Drug Administration approved ipilimumab (Yervoy), an anti–CTLA-4 antibody for metastatic melanoma.
New Chapter in Cancer Research
There is still a lot of uncertainty regarding how many and which patients will benefit from immunotherapies and for which cancers they will be most effective, according to the editors of Science. Still, the ongoing scientific investigations into identifying biomarkers that might offer answers and researching ways to make these therapies more potent, they said, show that a new chapter in cancer research has begun. ■
Reference
1. Couzin-Frankel J: Cancer immunotherapy. Science 342:1432-1433, 2013.
