Jim Allison and Tasuku Honjo’s Nobel Prize-winning contributions to cancer immunotherapy

James
P. Allison of MD Anderson Cancer Center and Kyoto University
Professor Tasuku Honjo in Kyoto jointly won the Nobel Prize in
physiology or medicine.
Reuters

• Cancer immunotherapy researchers Jim Allison and Tasuku Honjo
  have won the Nobel Prize in Physiology or Medicine for their work
  in cancer immunotherapy.
• Allison and Honjo’s work has led to the development and
  approval of medications that harness the body’s immune system to
  go after cancer. 
• “I was really just trying to understand the immune system,”
  Allison said of his research on Monday. It’s since gone on to be
  the basis for a blockbuster cancer drug to treat melanoma. 

At 6 a.m. Monday morning, Jim Allison was greeted at his hotel
room by friends and colleagues bearing bottles of
champagne. 

A half hour earlier, Allison, a scientist at the University
of Texas MD Anderson Cancer Center, had gotten the news that he
and Tasuku Honjo, a scientist at Kyoto University, had
jointly won the Nobel Prize in Physiology or Medicine for their
work in cancer immunotherapy. 

The two were instrumental in
bringing about a new
type of cancer treatment known as cancer immunotherapy.
Immunotherapy harnesses the power of the immune system to help it
identify and knock out cancerous cells.

Specifically, Allison and Honjo’s work has to do with
treatments known as checkpoint inhibitors. These drugs help take
the brake off the body’s immune system so that the body’s immune
system, through T cells, can attack cancer cells. 

Allison’s research led him to figure out how to block a protein
on the T cells, so that way they could go after cancer. Research
led to the creation of ipilipumab or Yervoy, approved in 2011
that kickstarted a renaissance for immunotherapies. 
Allison’s often dubbed the “godfather of cancer immunotherapy.”

Honjo’s work led him to discover how to target PD1 (short
for programmed cell death 1), the basis for drugs that
have been able to treat conditions like melanoma and lung cancer
and have been credited for making
President Jimmy Carter cancer-free. 

What the discoveries have done for the field

Today, the field of cancer immunotherapy is exploding. Some
of the drugs are blockbusters for companies like Merck and
Bristol-Myers Squibb, and it’s sparked additional research into
other ways to target the immune system,
including cell therapies. But that wasn’t how it all
started. 

“I was really just trying to understand the immune system,”
Allison said of his research at a press conference Monday at the
International Cancer Immunotherapy Conference in New York. While
he was studying as an undergraduate, researchers were just
starting to learn about the role T cells played in the immune
system.

“Jim is a dyed in the wool immunologist and always was,” Jill
O’Donnell Tormey, CEO of the Cancer Research Institute — an
organization at which Allison serves as director of its
scientific advisory council — told Business Insider. “His
interest in this was never in the thought of developing an
immunotherapy, it was about understanding T cell biology.” 

Tormey said that it took a lot to get the science from the
scientific discovery of figuring out how to block the protein on
T cells to a cancer treatment that’s been on the market
since 2011. 

“Nobody was interested in immunotherapy, drug companies didn’t
want to touch it with a 10-foot pole,” Tormey said. It took years
until Medarex, a company eventually acquired by Bristol-Myers
Squibb, started developing a treatment now known as ipilipumab,
or Yervoy. 

The history of cancer immunotherapy

Recent immunotherapy successes are far from the first time
researchers have explored using the immune system to fight
cancer.

In the 1890s a
doctor named William Coley treated his cancer patients by
infecting them with bacteria. The treatment worked for some of
them. With the immune system firing on all cylinders to knock out
invading bacteria, it could also take on the cancerous cells and
knock them out as well. That wouldn’t necessarily have happened
if the immune system wasn’t stimulated. 

At the time, very little was understood about the immune system,
and after Coley died, his methods stopped being used in favor of
radiation therapy. But in 1953, Coley’s daughter, Helen Coley
Nauts, founded the Cancer Research Institute, which works to
understand the relationship between cancer and the immune system.

In the 1970s, scientists pursued an immunotherapy using a
protein called tumor necrosis factor, or TNF, which the body
makes in response to foreign organisms in the body, including
bacteria and tumor cells.

Jan Vilcek, a microbiology professor at New York University and
one of the scientists who worked on developing a TNF treatment at
the time, told Business Insider
in 2015 that in animal testing, TNF was able to block the
growth of tumors. But when put into humans, the added TNF was so
toxic that it made people sick, even at doses that wouldn’t kill
tumors.

That was the end of immuno-oncology research for a
while, though
not the end of the story for TNF-related therapies.

Even so, the Cancer Research Institute stuck with it, and
eventually in 2011, the first immunotherapy called Yervoy was
approved in the US to treat melanoma. The drug helps the immune
system respond to cancerous cells by keeping it from pushing on
the brakes before it has a chance to kill the cells. Since then,
a number of other cancer treatments using the immune system have
been approved, with more still in development.

There have now been seven checkpoint inhibitors approved by
the FDA including
one approved last Friday to treat a form of skin cancer. Six
of them work on the proteins PD-1 and PD-L1, which are key in
telling the body’s immune system to react to a cancer cell or
not. 

See also: