In August 2015, the world learned that former U.S. president Jimmy Carter’s melanoma skin cancer had spread to his liver and his brain. Patients with melanoma that had spread through their bodies were expected to die from their disease, but doctors radiated Carter’s tumors and then gave him Keytruda, a checkpoint inhibitor. Three months later, there was no evidence of cancer anywhere in his 91-year old body.
In 2001, a young woman named Sharon Belvin had been told by her doctors that there were no long-term survivors from melanoma like hers that had spread to the liver and lungs, and the available treatments of radiation and chemotherapy would not be effective. She was told that a new drug called ipilimumab, a checkpoint inhibitor, was in its initial phase I trial, which was not even a test of whether it could cure cancer; it was only being tested to see if it was safe to give to human patients. If Sharon took it, she would be one of the first humans to have ever received the drug. She didn’t know if the drug would kill her, but she did know that if she didn’t take it, her melanoma most likely would be fatal. This brave woman chose to take the experimental drug and all of the melanoma cells in her body disappeared. Since then, follow-up data have shown that most likely she is protected from the melanoma ever returning for the rest of her life.
What is a Checkpoint Inhibitor?
Ipilimumab is the first checkpoint inhibitor drug that was developed by James Allison, a brilliant and rebellious scientist who grew up in Alice, Texas, a town so small that all the grades in elementary school were taught in the same room. For more than 30 years before James Allison started his research, scientists had known that everyone makes millions of cancer cells every day. Your immune system can recognize that cancer cells are different from normal cells, so it attacks and kills the cancer cells just like it kills invading germs. You develop cancer only when your immune system fails to recognize that the cancer cells are different from your normal cells. Then instead of being killed by your immune system, the cancer cells are able to multiply, develop into tumors, and spread through your body.
Your immune system has two types of killer lymphocyte cells:
• T cells that come from your thymus gland
• B cells that come from your bone marrow.
Before Jim Allison came along, scientists knew that the T cells recognize a cancer cell and pass on this information to the B cell to tell it to kill that cancer cell. So for many years, scientists spent time trying to increase the stimulator made by the T cell to teach the B cell to kill the cancer, but this never worked. Then Allison, working in a small lab in Smithville, Texas, said that all the world’s leading scientists were wrong. Instead of stimulating the stimulator, there was another approach. He showed that T cells also inhibit the B cell to prevent B cells from uncontrollably attacking everything, even the host. He had to fend off a lot of dubious scientists. who laughed at him and considered him an upstart, but he was correct. This new treatment for cancer includes inhibiting the inhibitor that the T cell sends to the B cell. By inhibiting the inhibitor produced by the T cell, the T cell could produce B cell stimulators without inhibition and they could kill the cancer cells.
These chemicals that block T cell inhibitors are called checkpoint inhibitors, and they are curing some patients with cancers that were formerly considered to be hopeless. In 2018, Jim Allison went to Stockholm to receive the Nobel Prize in Medicine for his discoveries, and today he is head of the largest cancer hospital in the world, MD Anderson Cancer Center in Houston, Texas.
The Future for Checkpoint Inhibitors
In 2011 the FDA approved ipilimumab, and it has been used to cure some hopeless cases of melanoma and advanced cancers of the lung, kidney, and bladder. Once a person is cured of cancer by checkpoint inhibitors, that person is thought to be protected from ever getting that cancer again. The problem facing the researchers was that sometimes checkpoint inhibitors make the immune system so powerful that it can attack and kill the patient.
The FDA has approved three second-generation checkpoint inhibitors, and scientists now also have cancer vaccines and adoptive T cell transfer, in which a patient’s own T cells are changed outside the body and then reinjected back into the bloodstream. Ipilimumab markedly reduces the cancer in 20 percent of stage-4 (usually fatal) melanoma patients, and two newer check point inhibitors and other drugs have improved this response rate to almost 50 percent. They are now being used to treat non–small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin’s lymphoma. They are being tested to treat brain, breast, ovarian, and prostate cancers.
Jim Allison’s Personal Interest in Cancer
Allison’s mother died of a cancerous lymphoma when he was just 10 years old, an uncle died of melanoma, and another uncle died of lung cancer. One week after his brother died of prostate cancer in 2005, Allison was diagnosed with prostate cancer himself at age 57. He had his prostate removed and has had no known recurrence, but he developed a melanoma in his nose at age 67.
Allison was raised in a small Texas town where kids usually did not go to college. His early work was largely ignored by the world’s top scientists, but today he is a Nobel Prize winner who is one of the most respected scientists in the world because of his revolutionary ideas about checkpoint inhibitors. He is the subject of a wonderful 2019 documentary film, Jim Allison: Breakthrough, that is widely available on the popular streaming services and is well worth watching. He breaks every stereotype of how a nerdy scientist is supposed to look and act, and can be seen in the documentary trailer playing his harmonica with Willie Nelson.
Inspiration from Jim Allison’s Quest to Cure Cancer
If you are dealing with a cancer diagnosis, make sure your doctor or team of doctors can explain all of the available options and help you decide if any of the recent advances or experimental treatments are appropriate for you.
Everyone, at any stage of life, can follow the lifestyle rules that can help to prevent and treat cancer:
• avoid smoking, alcohol, recreational drugs and other toxic substances
• avoid being overweight
• try to exercise every day
• eat a plant based diet that includes lots of vegetables, fruits, beans, whole (unground) grains, nuts and other seeds
• limit or avoid processed foods including all sugar-added foods and drinks including fruit juices, and fried foods
• limit or avoid meat from mammals and processed meats
• do not take hormones unless your doctor has a specific reason for prescribing them
• avoid excessive exposure to sunlight
James P. Allison
Born August 7, 1948
