The 2018 Nobel prize celebrates advances in cancer immunotherapy

Two immunologists — one from Texas, one from Japan — have been awarded the Nobel Prize in physiology or medicine for their pioneering research in cancer therapeutics. Their work is already saving lives and making it more likely that some cancer patients with advanced disease can fully recover.

James P. Allison, 70, is the chair of the department of immunology at MD Anderson Cancer Center in Houston, Texas. Tasuku Honjo, 76, is a distinguished professor at the Kyoto University Institute for Advanced Study in Japan.

Working in labs on different continents, both have made key discoveries over the past half-century that advanced the field of immunotherapy for cancer, a disease that still kills millions of people every year. They will share the $1 million prize, which was announced by the Nobel Prize Committee in Stockholm this morning.

Allison and Honjo’s research led to the rise of immunotherapy drugs; immunotherapies stimulate the immune system to help the body attack the disease from within. “The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer,” the Nobel Committee said in a statement.

Until very recently, most cancer patients only had a few options for treatment. They could get chemotherapy or radiation to try to kill the cancerous cells, or they could have surgery to cut out the cells. Yet these treatments can be blunt instruments, killing healthy cells along with cancerous ones. They also carry devastating side effects, and often fail in patients with late-stage disease.

Immunotherapy provides a new hope. Doctors have witnessed deadly tumors melt away, and patients who were supposed to die go into remission for years. These responses aren’t seen in every patient — only about 15 to 20 percent appear to benefit from immunotherapy, and we still don’t understand why. But very sick patients with cancer receiving chemotherapy just about never experience these kinds of amazing turnarounds. The new treatments can also be much more precise, targeting cancerous cells only instead of healthy tissue. That’s what makes immunotherapy so exciting — and Allison and Honjo’s work so important.

Allison and Honjo made discoveries that led to one of the most promising types of immunotherapy

Right now, many different kinds of immunotherapies for a variety of cancers are in clinical trials. These include treatments that use engineered viruses — HIV, measles, smallpox — to reprogram immune cells to destroy cancer. The types of immunotherapy that appear to be most promising at the moment — the ones that really have the medical community excited — are called “checkpoint inhibitors.” These harness the T-cells, a type of white blood cell known as the soldiers of the immune system, to attack cancer.

Allison and Honjo made key discoveries about checkpoint inhibitors that eventually led to the approval of numerous cancer checkpoint therapies for market.

One of the first approved checkpoint therapies was ipilimumab (brand name Yervoy), an intravenous infusion that came to market in 2011 and targets a protein called CTLA-4. Allison studied CTLA-4. “He was one of several scientists who had made the observation that CTLA-4 functions as a brake on T cells,” the Nobel Committee said in a statement. “Despite little interest from the pharmaceutical industry, Allison continued his intense efforts to develop the strategy into a therapy for humans.”

By 2010, some patients with advanced melanoma saw their cancer disappear when using drugs that emerged from this research in clinical trials. “Such remarkable results had never been seen before in this patient group,” the committee said.

Meanwhile, Honjo discovered PD-1, another important checkpoint inhibitor. He “eventually revealed that it also operates as a brake,” the Nobel Committee said. “Therapies based on his discovery proved to be strikingly effective in the fight against cancer.”

Indeed, drugs targeting PD-1 — such as nivolumab and pembrolizumab (which Jimmy Carter used for his cancer and prolonged his life) — have been approved for the market. These drugs can treat advanced melanoma and lung cancer. The PD-1 targeting approach has also shown promise in a variety of other cancers, such as kidney and bladder cancers and Hodgkin lymphoma.

Elusive and costly cancer cures

While the discovery of immunotherapies for cancer is the most exciting thing to happen in oncology in the past half-century, we’re still a long way from curing the disease. The dramatic progress in immunotherapies has been the simple fact that these drugs work extremely effectively for some periods of time in some patients for some cancers. But one of the major challenges is to understand why, and who will benefit.

Dr. Michael Postow, an oncologist who is researching immunotherapies at Memorial Sloan Kettering, told Vox in 2015 that for all the buzz about these drugs right now, there’s a lot to be learned: “As excited as we are about this field, we know it doesn’t help every patient, and we’re still trying to figure out who it helps, how it helps, and why.”

There’s also the cost issue: cancer immunotherapies can cost upwards of $100,000 per person— and they’re not always adequately covered by insurers. “If the affordability of drugs is not addressed soon,” a recent Nature article warned, “many people with cancer might not be able to reap the rewards of cutting-edge therapies.”

So we’re still in the very early days for immunotherapy — including figuring out how to address access barriers. But undoubtedly, the work of Allison and Honjo directed doctors closer to elusive cancer cures.

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