For years there have been three tools to fight cancer: burn it out with radiation, inject poisons that are hoped to kill the cancer without killing the patient, and/or cut it out. There's increasing interest in a fourth way, one that doesn't hurt the patient, but instead causes the patient's immune system to get in the fight.
Cancer is the uncontrolled growth of abnormal cells. And somehow the cancer cells turn of the patients immune response to this attack. While it might seem like common sense, it took over a century for the theory of turning off cancer's immune system kill switch to really catch on.
And now the 2018 Nobel Prize in Physiology or Medicine is being awarded jointly to James P. Allison and Tasuku Honjo who have have advanced research on the topic remarkably. Press release: The Nobel Prize in Physiology or Medicine 2018 tells us what each of them did:
About Allison:
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.
About Honjo:
In 1992, a few years before Allison’s discovery, Tasuku Honjo discovered PD-1, another protein expressed on the surface of T-cells. Determined to unravel its role, he meticulously explored its function in a series of elegant experiments performed over many years in his laboratory at Kyoto University. The results showed that PD-1, similar to CTLA-4, functions as a T-cell brake, but operates by a different mechanism (see Figure). In animal experiments, PD-1 blockade was also shown to be a promising strategy in the fight against cancer, as demonstrated by Honjo and other groups. This paved the way for utilizing PD-1 as a target in the treatment of patients. Clinical development ensued, and in 2012 a key study demonstrated clear efficacy in the treatment of patients with different types of cancer. Results were dramatic, leading to long-term remission and possible cure in several patients with metastatic cancer, a condition that had previously been considered essentially untreatable.
Wow. Simply beefing up a person's own immune system can beat back cancer. There have been many false positives in the search for the magic bullet. But this one is plausible enough that it might actually work.
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2:27 PM 12/10/2018
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