2018 Nobel Price Cancer

The Nobel Prize in Physiology or Medicine was awarded on Monday to James P. Allison of the United States and Tasuku Honjo of Japan for their work on unleashing the body’s immune system to attack cancer, a breakthrough that has led to an entirely new class of drugs and brought lasting remissions to many patients who had run out of options.

Their success, which came after many researchers had given up on the idea, “brought immunotherapy out from decades of skepticism,” said Dr. Jedd Wolchok, a cancer specialist at Memorial Sloan Kettering Cancer Center in New York. It has, he said, “led to human applications that have affected an untold number of people’s health.”

Before Dr. Allison’s and Dr. Honjo’s discoveries, cancer treatment consisted of surgery, radiation, chemotherapy and hormonal treatments. A statement from the Nobel committee hailed their accomplishments as establishing “an entirely new principle for cancer therapy.”

The drugs based on their work belong to a class called checkpoint inhibitors, with tongue-twisting names that have nonetheless become familiar to many patients. The first ones approved were ipilimumab (brand name Yervoy), nivolumab (Opdivo) and pembrolizumab (Keytruda). Others have since come to market.

Earlier attempts by other researchers to recruit the immune system to fight cancer sometimes worked but more often did not. Dr. Allison and Dr. Honjo succeeded where others had failed by deciphering exactly how cells were interacting so they could fine-tune methods to control the immune system.

Checkpoint inhibitors do not work for everyone and they have only been approved for some cancers. They can have severe side effects, and they are expensive, costing more than $100,000 a year. But the approach, known as immunotherapy, has become a mainstay of treatment for a number of types of cancer, and a great deal of research is underway — including work by Dr. Allison and Dr. Honjo — to find the best ways of combining checkpoint inhibitors with one another and with standard treatments to help more patients.

The checkpoint inhibitors now on the market are used for cancers of the lung, kidney, bladder, head and neck; for the aggressive skin cancer melanoma; and for Hodgkin lymphoma and other cancers.

Attacking Cancer Cells

Doctors are using immunotherapy to help the cells of the immune system recognize and attack cancer cells.

T-CELLS

T-cells are a type of white blood cell that can identify and kill infected, damaged or cancerous cells. Each T-cell has clawlike receptors on its surface that can recognize and lock onto antigens, foreign or abnormal protein fragments on the surface of infected or cancerous cells.

ACTIVATING A T-CELL

The T-cell must be activated before it can find and attack cancer cells. A specialized cell presents the T-cell with an antigen from a cancer cell, along with a co-stimulator protein. The T-cell begins to hunt down and kill any cells that are covered with the same antigen.

CANCER AND CHECKPOINTS

Cancer cells can avoid destruction by taking advantage of a switch on the T-cell called an immune checkpoint. The checkpoint can shut down the T-cell and suppress the immune response, allowing the cancer to grow undisturbed.

CHECKPOINT INHIBITORS

Drugs known as checkpoint inhibitors can physically block the checkpoint, which frees the immune system to attack the cancer. A single T-cell can kill thousands of cancer cells.

Dr. Honjo, 76, is a longtime professor at Kyoto University, where he did his landmark work. Previously, he did research at Osaka University, the University of Tokyo and the National Institutes of Health in Washington.

Dr. Allison, 70, is chairman of immunology at the University of Texas M.D. Anderson Cancer Center. He did the work recognized by the Nobel committee while working the University of California at Berkeley and Memorial Sloan Kettering Cancer Center in New York.

“When I’m thanked by patients who recover, I truly feel the significance of our research,” Dr. Honjo said during a news conference at the Japanese university, according to Japanese news reports. He added: “I’d like to continue researching cancer for a while so that this immunotherapy will help save more cancer patients than ever before.”

In a telephone interview, Dr. Allison said that when checkpoint inhibitors work, patients “are good to go for a decade or more.” He said he was working with other researchers, including his wife, Dr. Padmanee Sharma, an oncologist at MD Anderson, to understand the mechanisms so the treatments would help more patients.

“It’s a big challenge,” Dr. Allison said. “But we know the basic rules now. It’s just a matter of more hard work to put things together based on science.”

Dr. Allison said he first heard about the prize via calls and texts from family, friends and colleagues who had seen news reports, before the Nobel committee could reach him. He was in New York, and the committee did not have his cellphone number.

Dr. Allison and Dr. Honjo, working separately, showed in the 1990s how certain proteins act as “brakes” on the immune system’s T-cells and limit their ability to attack cancer cells. Suppressing those proteins, they theorized, could transform the body’s ability to fight cancer.

T-cells, a type of white blood cell, are sometimes called the soldiers of the immune system. They are deployed to fight infections and cancer, but malignant cells can elude them. The T-cells carry molecules called checkpoints, that the body uses to shut the cells down when it needs to stop them. Cancer cells can lock onto those checkpoints, crippling the T-cells and preventing them from fighting the disease.

* source New York Times

https://www.nobelprize.org/uploads/2018/10/press-medicine2018.pdf