Published On: Tue, Oct 2nd, 2018

“She got the drug – and the cancer just disappeared”

About a year ago, the Nobel Prize laureate, Prof. James Allison, was interviewed by Yedioth Ahronoth and revealed how he developed the method that shook the medical world: "I did not do my research to cure cancer, I tried to understand the immune system in depth"

Am illustration of James P Allison and Tasuku Honjo provided by the Nobel Assembly. Photograph: Nobel Assembly

The Nobel Prize in Physiology or Medicine has been awarded to James P. Allison and Tasuku Honjo for discoveries that led to a new way to treat cancer by targeting the body’s immune system rather than the tumor.

But, when Professor Allison, was asked in an interview with Yedioth Ahronoth a year ago to demonstrate the power of the method he developed, he told the unbelievable.

Twelve years ago, Allison met a young woman who had just about to die of cancer. The doctors tried to treat her in every possible way, but nothing helped,” said the American researcher to the Israeli newspaper.

Fortunately for her, one of her doctors suggested that she take part in the experiment with a revolutionary drug based on a new idea, which was studied by Prof. Allison and was in the initial stages of development. “She got the new drug, and her cancer just disappeared,” he described the dramatic result. “When the young woman arrived for her first annual follow-up checkup, her doctor asked her if she wanted to meet the man who had invented her medicine. We met with her husband and parents and we began to hug and cry. ”

After more than 25 years in which no metastatic melanoma drug was found, it was approved by the US Food and Drug Administration as the first treatment of the deadly disease. More than a decade since the start of the experiments, some of the patients, who were then in a terminal condition, are still alive.

Watch him explain about his work:

The discovery of the Nobel Prize winners is definitely a revolution, “says Prof. Nir Peled, director of the oncology department at Soroka.” Mobilization of the immune system in the war against cancer has changed the entire therapeutic concept and it has become part of the practical treatment program in a way that no one dreamed of.

This change not only changed the nature of the treatments but also enabled some patients to be cured completely, despite metastases that spread throughout the body. ”

“We are only at the beginning of an era,” Prof. Peled adds, “we are studying today to engineer the immune system because of the insights they have established.” I believe that in 10 years, a significant portion of cancer treatments will be based on this treatment.

The drugs that mobilize the immune system to attack the cancer was the first of a wave of breakthrough drugs, known as Immunotherapy, for which the prestigious award was now awarded.

When the body’s immune system works properly, a group of white cells called T cells searches for foreign invaders in the body, such as cancer cells, and works to destroy them. But in some cases, these cells do not work properly. The new drug, which has been approved to date, clings to healthy immune cells, altering their activity and helping them destroy cancer cells.

“I understood that we do not know enough about the activity of T cells and that the basis for success is to understand in depth their mechanism of action,” Allison told Yedioth Ahronoth. “I tried to understand what turns these cells on and off, Something related to cancer research itself. ”

Allison decided not to repeat the mistakes others had made before him. “The turning point came after we understood a few things about what activates the cells of the immune system, and we realized that, like in the car, it is not enough to turn the key on the switch so that it will go.

© The Nobel Committee for Physiology or Medicine discovery 2018. Illustrator Mattias Karlén/

What astonished him, Allison said, was the understanding that in order to fight cancer, the immune system had to be treated, not the tumor itself. “There is no need to develop a different drug for each tumor, because the cancer cell itself does not matter, and the immune system does not care whether the tumor has a genetic mutation or that it works to destroy it regardless of mutation.  They have been doing this for the rest of their lives, as opposed to other drugs, whose activity wears off when they are stopped. ”

It is difficult to connect the modest, plainly dressed professor with the heavy southern accent to one of the most important revolutions of the medical world in recent years. Allison, the son of a doctor who grew up in a small town in South Texas, became interested in medicine as a child. At a young age, he decided to become a scientist. “I did not do what I did to cure cancer,” he said. “I tried to understand the immune system in depth and how it works. The better understanding of the mechanism of cancer was born of the scientific knowledge accumulated about the body’s immune system activity. ”

By Sarit Rosenblum and Dr. Itay Galforsam, Ynet News

The announcement:

Press release
2018-10-01

The Nobel Assembly at Karolinska Institutet

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

SUMMARY
Cancer kills millions of people every year and is one of humanity’s greatest health challenges. By stimulating the inherent ability of our immune system to attack tumor cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy.

James P. Allison studied a known protein that functions as a brake on the immune system. He realized the potential of releasing the brake and thereby unleashing our immune cells to attack tumors. He then developed this concept into a brand new approach for treating patients.

In parallel, Tasuku Honjo discovered a protein on immune cells and, after careful exploration of its function, eventually revealed that it also operates as a brake, but with a different mechanism of action. Therapies based on his discovery proved to be strikingly effective in the fight against cancer.

Allison and Honjo showed how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer. The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer.

Can our immune defense be engaged for cancer treatment?

Cancer comprises many different diseases, all characterized by uncontrolled proliferation of abnormal cells with capacity for spread to healthy organs and tissues. A number of therapeutic approaches are available for cancer treatment, including surgery, radiation, and other strategies, some of which have been awarded previous Nobel Prizes. These include methods for hormone treatment for prostate cancer (Huggins, 1966), chemotherapy (Elion and Hitchins, 1988), and bone marrow transplantation for leukemia (Thomas 1990). However, advanced cancer remains immensely difficult to treat, and novel therapeutic strategies are desperately needed.

In the late 19th century and beginning of the 20th century the concept emerged that activation of the immune system might be a strategy for attacking tumor cells. Attempts were made to infect patients with bacteria to activate the defense. These efforts only had modest effects, but a variant of this strategy is used today in the treatment of bladder cancer. It was realized that more knowledge was needed. Many scientists engaged in intense basic research and uncovered fundamental mechanisms regulating immunity and also showed how the immune system can recognize cancer cells. Despite remarkable scientific progress, attempts to develop generalizable new strategies against cancer proved difficult.

Accelerators and brakes in our immune system

The fundamental property of our immune system is the ability to discriminate “self” from “non-self” so that invading bacteria, viruses and other dangers can be attacked and eliminated. T cells, a type of white blood cell, are key players in this defense. T cells were shown to have receptors that bind to structures recognized as non-self and such interactions trigger the immune system to engage in defense. But additional proteins acting as T-cell accelerators are also required to trigger a full-blown immune response (see Figure). Many scientists contributed to this important basic research and identified other proteins that function as brakes on the T cells, inhibiting immune activation. This intricate balance between accelerators and brakes is essential for tight control. It ensures that the immune system is sufficiently engaged in attack against foreign microorganisms while avoiding the excessive activation that can lead to autoimmune destruction of healthy cells and tissues.

A new principle for immune therapy

During the 1990s, in his laboratory at the University of California, Berkeley, James P. Allison studied the T-cell protein CTLA-4. He was one of several scientists who had made the observation that CTLA-4 functions as a brake on T cells. Other research teams exploited the mechanism as a target in the treatment of autoimmune disease. Allison, however, had an entirely different idea. He had already developed an antibody that could bind to CTLA-4 and block its function (see Figure). He now set out to investigate if CTLA-4 blockade could disengage the T-cell brake and unleash the immune system to attack cancer cells. Allison and co-workers performed a first experiment at the end of 1994, and in their excitement it was immediately repeated over the Christmas break. The results were spectacular. Mice with cancer had been cured by treatment with the antibodies that inhibit the brake and unlock antitumor T-cell activity. Despite little interest from the pharmaceutical industry, Allison continued his intense efforts to develop the strategy into a therapy for humans. Promising results soon emerged from several groups, and in 2010 an important clinical study showed striking effects in patients with advanced melanoma, a type of skin cancer. In several patients signs of remaining cancer disappeared. Such remarkable results had never been seen before in this patient group.

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