n the day I arrive at MD Anderson Cancer
Center in Houston to meet James Allison
and his longtime collaborator Padmanee
Sharma, they are nowhere to be found.
The previous day, one of their colleagues
informs me, Allison was summoned up
on stage by Willie Nelson, in front of
60,000 people at a rock festival in Austin, to deliver a harmonica solo. They are
still on their way back.
By now, Allison is almost used to adulation. There are even murmurings that
his work in cancer immunotherapy might
win him the Nobel Prize. Twenty years
ago, he was the first to show it’s possible to
turbocharge the body’s response to cancer
with a drug that releases the immune system so that it destroys tumors on its own.
The drug he identified to do that, called
Yervoy, went on sale in 2011 to treat metastatic skin cancer. In lucky patients, it
causes otherwise fatal tumors to melt away.
By last year, worldwide sales of Yervoy and
two newer drugs had reached $6 billion a
year, and the medications had been given
to more than 100,000 people. This transformative new class of immunotherapy
agents, known as checkpoint inhibitors, is acknowledged to be
the most important advance against cancer since chemotherapy.
Allison, who is 68, is an unimposing man, with a slight Texas
drawl and a stringy mane of white hair. He still finds it hard not to
cry when he meets cancer survivors saved by his discovery. But I
had gone to talk to him about unfinished business. That is because
for every miracle cure, for every Jimmy Carter or 22-year-old
melanoma patient pulled back from death, there are many more
people who, for reasons that no one understands, can’t be saved.
Of all patients dying from all types of cancer in America this year,
only one in 12 would be expected to benefit from any immunotherapy drug. Some even argue that direct-to-consumer marketing,
including a Super Bowl ad, has created dangerous expectations.
Patients cashing in their last chance will, more likely than not,
find themselves among the large majority for whom drugs like
Allison’s don’t yet work.
Allison has known about the shortcomings longer than any-
one. He says they dampen any sense of triumph and shadow him
at award banquets. Sometimes, he stays awake at night. “About
22 percent of melanoma patients that get a single round of treat-
ment with Yervoy are alive 10 years later,” he said after receiving
a Lasker Award in 2015, and then added solemnly: “We got to get
that up, and we got to do it in more kinds of cancer.”
At MD Anderson I was introduced to what Allison calls the
“platform.” It is a large-scale e;ort to determine why the immune
system at times acts like the perfect weapon but in other cases fails
to kick into action. Sharma, a Guyanese immigrant and practicing
cancer doctor, oversees the collection of tumor samples from 100
of Anderson’s 165 cancer trials that involve immunotherapy. The
tissue is then scrutinized by her lab and Allison’s for clues to how
the battle is proceeding. “What is the immune response doing that
leads to tumor rejection? What is the immune response doing that
it stops rejecting the tumor and [it] starts growing again?” Sharma
asks. “Those are big questions that we still need to understand.”
The answers can’t come too soon for some. The pharmaceutical
industry and research institutions are in the midst of a pell-mell
sprint into thousands of clinical trials based on new immunother-
apy agents. As of October, by one tally, more than 166,736 patients
were being sought to fill slots in studies of drugs involving a single
protein, called PD- 1. The overall number of immunotherapy trials
probably tops 3,000, says Je; Bluestone, an immunologist at the
University of California, San Francisco, who also serves as presi-
dent and CEO of the Parker Institute for Cancer Immunotherapy.
But a growing number of researchers fret that the flood of
clinical trials is uncoördinated, redundant, and potentially counterproductive. That is because in many cases, the basic science
remains little understood. “This is not sustainable,” Ira Mellman,
the keynote speaker at the annual meeting of the Society for
A Time Line
Over 150 years,
doctors learned to
treat cancer with
vaccines. Immunotherapy is the
latest weapon in