Two researchers whose work sparked a revolution in cancer treatment have won the Nobel Prize in Physiology or Medicine this year. Tasuku Honjo currently at Kyoto University in Japan and James Allison now at the University of Texas MD Anderson Cancer Center in Houston separately discovered how to use the body's own immune system to fight cancer.
Allison and Honjo are now both in their 70s. In the 1990s, their research on the basic biology of the human immune system led to a class of drugs called checkpoint inhibitors, reports Joe Neel for NPR. These drugs lift restrictions the immune system and allow immune cells to attack and destroy cancer cells. Not all cancers can be treated by checkpoint inhibitors but for those that can, the results are striking.
Checkpoint inhibitors currently available to patients can be used to treat lung, kidney, bladder, head and neck cancers as well as aggressive skin cancer and Hodgkin lymphoma, reports Denise Grady for The New York Times. When the treatments work, the cancer goes into remission. Allison tells The Times that patients are "good to go for a decade or more."
"It represents a completely new principle, because unlike previous strategies, it is not based on targeting the cancer cells, but rather the brakes — the checkpoints — of the host immune system,” says Klas Kärre, a member of the Nobel Committee and an immunologist at the Karolinska Institute in Stockholm, according to a Nature article by Heidi Ledford and Holly Else. “The seminal discoveries by the two laureates constitutes a paradigmatic shift and a landmark in the fight against cancer.”
T-cells, a kind of white blood cell that fights infections, carry proteins called checkpoints that the body uses to set the T-cells into attack mode or not. Cancer cells can latch onto these checkpoints, allowing the malignant cells to go unnoticed.
In his lab based at the University of California, Berkeley at the time, Allison's work focused on a checkpoint protein called CTLA-4, a press release from the Nobel committee explains. Allison's team created a drug that could stick to CTLA-4 and prevent it from working. This essentially took the brakes off T-cells and allowed them to attack cancer cells. In 2010, Allison tested this drug in a clinical trial with people who had advanced melanoma. The skin cancer disappeared in several cases.
Independently, Honjo had discovered PD-1, another protein in T-cells. Working in his lab at Kyoto University, Honjo's team figured out how to block PD-1 and unleash T-cells in a different way. Their drug showed dramatic success in patients treated in 2012, including giving long-term remission to people with metastatic cancer. Experts previously thought that metastasis, when the cancer spreads to other organs and tissues, was untreatable, the Nobel committee's press release explains.
Allison heard the news of his Nobel prize win while at an immunology conference in New York City, reports Ledford and Else. Colleagues arrived at his hotel room with champagne at 6:30 a.m. in the morning to celebrate. Honjo assembled his team in the lab to enjoy the recognition.
"When I'm thanked by patients who recover, I truly feel the significance of our research,” Honjo said during a news conference at the Japanese university, reports Grady for The New York Times. "I’d like to continue researching cancer for a while so that this immunotherapy will help save more cancer patients than ever before.”
Currently, many of the drugs on the market are expensive and have side effects, reports Karen Weintraub for Scientific American. Hundreds of clinical trials are currently underway to test CTLA-4, PD-1 and other drugs that use the immune system to fight various cancers.