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comes of age
Oncologists have long rested their treatment plans on three so-called “pillars”—chemotherapy, surgery, and radiation. But in
recent years, scientists have been busily erecting a fourth pillar:
immunotherapy. The idea of harnessing the immune system to
fight cancer has already moved from the lab to the clinic, thanks
to technologies such as checkpoint inhibitors and genetically
engineered immune cells. By Amber Dance
Fifteen years ago, Renier Brentjens returned from a vacation and rushed to his lab at Memorial Sloan Kettering Cancer Center in New York. A month earlier, he’d treated mice with
genetically engineered immune cells that he hoped would combat
cancer. And when he got to the lab, he found that all of the mice
were still alive.
Amazed, Brentjens thought to himself, “This stuff might actually work.” And it did—in 2013, he and his colleagues reported that
they used this kind of cell therapy to treat five people with B-cell
acute lymphoblastic leukemia, and all five achieved total remission, though one later relapsed. That success ignited a “firestorm”
in the development of engineered immune cells, says Brentjens.
The idea behind immunotherapy is to harness the system the
body normally uses to attack pathogens and encourage it to go
after cancerous cells instead. The field has exploded in recent
years, with approval of a handful of medications and nearly 1,500
cancer immunotherapy trials listed on the U.S. National Institutes
of Health Clinical Trials.gov registry.
Two approaches getting plenty of attention are checkpoint
inhibitors and modified cells known as “chimeric antigen receptor (CAR) T cells.” The former approach takes the brakes off of
anticancer immune cells. The latter, used by Brentjens, involves
genetically engineering immune cells to allow them to home in on
But those are just two of many ideas under the immunotherapy
umbrella, which also includes approaches such as vaccines.
Those developing such therapies use a variety of techniques and
tools, including antibodies, gene editing, and viral gene transfer.
Unfortunately, these treatments don’t usually work for all cancers,
and can cause serious side effects and even death—meaning
there is still plenty of work to do to improve them and to eliminate
The answer to all cancers?
While one should be cautious about the word “cure,” there are
certainly patients from early trials who are still alive 10 years later
with apparently little or no cancer in their bodies, according to
Alan Korman, vice president of immuno-oncology discovery at
Bristol-Myers Squibb in Redwood City, California, who has been
involved with developing two of the checkpoint inhibitors now on
the market, nivolumab and ipilimumab.
Indeed, cancer immunotherapy is not a new idea. The late-
19th century surgeon William Coley found that deliberately
inducing bacterial infections in his patients could sometimes
mysteriously eliminate cancer. Though he didn’t understand
how at the time, it’s now believed that the bacteria or bacterial
products Coley used activated his patients’ immune systems. As
radiation—which was easier to apply and offered more consistent
results—became a popular therapy, Coley’s toxins fell by the
Another early hint of immunotherapy’s potential came in the
late 20th century, when clinical trials showed that treating mela-
noma with interleukin-2 (IL-2), an immune cell regulator, yielded
survival beyond five years for many patients.
In the bodies of many people with cancer, there are already
immune cells that can recognize and attack the tumor. But
tumors defend themselves by producing compounds that activate
biological “checkpoints” to stifle those protective cells. ILLUS
Cell culture: 3D cell/organelle culturing—April 7 Systems biology: Metabolome—May 12 Genomics: Microbiome—May 19