Immunotherapy innovator Jim Allison’s Nobel purpose

On the first day of October this year, the first Nobel Prize given for a cancer therapy in 28 years went to the first MD Anderson Cancer Center scientist to receive the world’s most pre-eminent award for outstanding discoveries in life sciences and medicine.

It was around 4:30 a.m. in Houston when Thomas Perlmann, secretary of the Nobel Committee for Physiology or Medicine, made the announcement in Stockholm:

"The Nobel Assembly at Karolinska Institute has today decided to award the 2018 Nobel Prize in Physiology or Medicine jointly to James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation."

Jim Allison, Ph.D., chair of Immunology and executive director of the immunotherapy platform, pioneered a revolutionary cancer treatment that frees the immune system to attack tumors.

“By stimulating the ability of our immune system to attack tumor cells, this year’s Nobel Prize laureates have established an entirely new principle for cancer therapy,” Perlmann noted in announcing the award to Allison, who shares the prize with Tasuku Honjo, M.D., Ph.D., of Kyoto University in Japan.

Taking the brake off T cells

The Nobel Prize recognizes Allison’s breakthrough work with T cells, the “soldiers” of the immune system that battle invaders and abnormal cells like cancer, bacteria and viruses. While T cells are fierce opponents of disease, they don’t attack every invader that comes along. If they did, the body would be in a constant state of fever, rash, inflammation or other immune system response. “Brakes” on the immune system prevent T cells from attacking everything, which is, in part, how cancer is able to develop.

Allison showed that the protein CTLA-4, which is found on the surface of T cells, acts as a brake — a type of immune system checkpoint the body uses to avoid a dangerously over-reactive immune response. He then developed an antibody to block CTLA-4’s “braking” action, freeing T cells to attack cancer.

His work and determination led to the development of Ipilimumab, the first in a class of drugs known as checkpoint inhibitors. In 2011, the drug — commercially named Yervoy — was approved for late-stage melanoma by the Food and Drug Administration. It has yielded unprecedented results. Twenty percent of patients with advanced melanoma who took the drug now live for at least three years, and many live 10 years and beyond.

Subsequent research has focused on other immune system “brakes,” most prominently PD-1 and PD-L1, with drugs approved to treat certain types and stages of cancers such as melanoma, lung, kidney, bladder, gastric, liver, cervical, colorectal, head and neck and Hodgkin’s lymphoma. Clinical trials are underway in many other cancer types.

The power of curiosity

“I never dreamed my research would take the direction it has,” says Allison, whose mother died of lymphoma was he was just 10. “It’s a great, emotional privilege to meet cancer patients who’ve been successfully treated with immune checkpoint blockade. They are living proof of the power of basic science, of following our urge to learn and to understand how things work.”

One of the most exciting aspects of immunotherapy, Allison says, is that it appears to continue working even after the treatment has stopped.

“The immune cells remain in the body. If the cancer comes back, the immune cells attack it.”

Allison says immunotherapy is quickly becoming the “fourth pillar” of cancer therapy, joining long-established treatments of surgery, radiation and chemotherapy.

“Immunotherapy won’t replace these other three, but it can be used in combination with them to offer patients the best chance to beat their disease.”

Allison will be honored at Nobel Prize ceremonies in Stockholm in December. The Nobel Prize in Physiology or Medicine has been awarded 108 times to 214 Nobel Laureates between 1901 and 2017.

Allison’s start in science

The son of a country doctor, Allison grew up in Alice, Texas, seemingly destined for medical school.

A lifelong interest in understanding how things work, and observing his father practicing medicine day-in and day-out, led to a decisive conclusion.

“I had a pretty good look at what it’s like to be a physician. As a doctor, you can’t make mistakes, you have to always be right,” Allison says. “Scientists generate and test hypotheses, which are wrong most of the time, otherwise you’re not asking the hard questions. Scientists only need to be right some of the time — preferably about important things.”

He shifted out of pre-med studies at The University of Texas at Austin, took a degree in microbiology and then went on to earn his doctorate in biological sciences in 1973.

Since then, Allison has been right often enough about important things to have a major impact in medical care — an impact that has saved the lives of countless cancer patients.

“Jim Allison’s research has led to life-saving treatments for people who otherwise would have little hope,” says Peter WT Pisters, M.D., president of MD Anderson. “The significance of immunotherapy as a form of cancer treatment will be felt for generations to come.”

First stop: Smithville

Allison started his career at MD Anderson in 1977, arriving as one of the first employees of the institution’s Science Park, a new basic science research center located in Smithville, Texas, where he made his first major discoveries. He was recruited back to MD Anderson in 2012 to lead the Immunology Department and to establish an immunotherapy research platform for MD Anderson’s Moon Shots Program™. In between came prominent positions as the leader of the immunology programs at the University of California, Berkeley, and Memorial Sloan-Kettering Cancer Center in New York.

“Science advances are the efforts of many,” Allison says. “A succession of graduate students, postdoctoral fellows and colleagues at MD Anderson, the University of California, Berkeley, and Memorial Sloan Kettering Cancer Center played important roles in this research.”

Allison’s ongoing leadership at MD Anderson focuses on improving knowledge of how these immune checkpoint inhibitors work in order to extend the benefits of immunotherapy to more patients with more types of cancer. He research continues, with his attention aimed at the details of immune response to cancer and identifying new targets for potential treatment.

There’s still work to be done

Under his leadership, with Scientific Director Padmanee Sharma, M.D., Ph.D., the immunotherapy platform conducts immune monitoring by analyzing tumor samples before, during and after treatment, in order to understand why these drugs work for some patients but not all. The platform works with more than 100 immunotherapy clinical trials at MD Anderson that are addressing a variety of cancers. The platform also collaborates with pharmaceutical companies to help them develop new drugs and combinations to better treat cancer.

“We need these drugs to work for more people,” Allison says. “One challenge is that the clinical success has outrun our scientific knowledge of how these drugs work and how they might best be combined with other therapies to improve treatment and reduce unwanted side effects. We need more basic science research to do that.”

Allison has collaboratively worked with scientists around the globe to expand the field of immunotherapy. He is a co-leader of the Stand Up To Cancer-Cancer Research Institute Cancer Immunology Dream Team and MD Anderson’s director of the Parker Institute for Cancer Immunotherapy (PICI). Allison also is deputy director of the David H Koch Center for Applied Research of Genitourinary Cancers at MD Anderson and holds the Vivian L. Smith Distinguished Chair in Immunology.

Crucial funding for his research over the years has come from the National Institutes of Health, particularly the National Cancer Institute, the Cancer Prevention & Research Institute of Texas, Howard Hughes Medical Institute, the Cancer Research Institute, Prostate Cancer Foundation, Stand Up To Cancer and PICI.

Allison’s major awards and accomplishments

1948
Born Aug. 7 in Alice, Texas

1969
Earns a bachelor of science degree in microbiology from The University of Texas at Austin

1973
Earns his doctorate in biological sciences

1977
Allison takes his first faculty position at MD Anderson’s Science Park in Smithville, Texas, where he develops a research interest in T cells.

1982
In his first major finding, at Smithville, Allison identifies the protein structure of the T-cell receptor, the previously mysterious ignition switch for immune response, with papers in the Journal of Immunology and Cell.

1984
Allison is recruited by the University of California, Berkeley, to lead its immunology department.

1992
At Berkeley, Allison publishes a paper in Nature that proves CD28, a molecule on the surface of T cells, acts as the gas pedal for the immune system.

1995
In a paper in the Journal of Experimental Medicine, Allison Shows that the protein CTLA-4 acts as a brake on T cells, halting immune response.

1996
Reports in a Science paper that blocking CTLA-4 with an antibody unleashes an immune response against cancer in experimental models, curing 90 percent of cases

1997
Named of the prestigious National Academy of Sciences and an investigator of the Howard Hughes Medical Institute

2004
Becomes chair of the Immunology Program at Memorial Sloan-Kettering Cancer Center in New York

2011
The Food and Drug Administration approves the anti-CTLA-4 antibody ipilimumab, now known as Yervoy, for treatment of late-stage melanoma after the drug becomes the first to extend the survival of these patients.

2012
Allison returns to MD Anderson to lead the Immunology Department and the new immunotherapy platform. The institution invests $40 million in the platform, including a $10 million recruitment grant from the Cancer Prevention and Research Institute of Texas.

Named co-leader of a national Dream Team of cancer immunotherapy researchers by Stand Up to Cancer and the Cancer Research Institute.

2013
Wins first AACR-CRI Lloyd J. Old-CRI Award in Cancer Immunology given by the American Association of Cancer Research, the world’s pre-eminent organization for cancer scientists.

The journal Science names cancer immunotherapy its 2013 Breakthrough of the Year.

2014
Allison, along with Tasuku Honjo, M.D., Ph.D., of Kyoto University’s Faculty of Medicine in Japan, wins the first Tang Prize for Biopharmaceutical Science.

2015
Wins the Lasker-DeBakey Clinical Medical Research Award, the nation’s highest honor for clinical research.

2016
Allison becomes MD Anderson director of the Parker Institute for Cancer Immunotherapy, a new $250 million effort by social media billionaire Sean Parker to advance the field.

Is named to Blue Ribbon Panel to advise the National Cancer Institute in its work with Vice President Joe Biden’s National Cancer Moonshot.

2017
Is included on Time magazine’s list of “The 100 Most Influential People”

Other honors

2017
The inaugural Sjoberg Prize from the Sjoberg Foundation and the Royal Swedish Academy of Sciences

The Wolf Prize for Medicine awarded in Israel by the Wolf Foundation; the Warren Alpert Foundation Prize and the International Balzan Foundation Prize.

2018
Albany Medical Center Prize in Medicine and Biomedical Research

The Jessie Stevenson Kovalenko Medal from the National Academy of Sciences

The BBVA Foundation Frontiers of Knowledge Award in Biomedicine

The King Faisal Prize for Medicine from the King Faisal Foundation

Dr. Paul Janssen Award for Biomedical Research from Johnson & Johnson

The Albany Medical Center Prize in Medicine and Biomedical Research.