Her medical file read 'death imminent.' His treatment plan changed cancer forever. | Opinion
Four decades ago, Dr. Steven Rosenberg saved the life of a 33-year-old Navy officer. Today, immunotherapy is the brightest new weapon in the fight against cancer.
In August 2015, former President Jimmy Carter thought he had mere weeks to live. His skin cancer ‒ metastatic melanoma ‒ had seeded malignant tumors in his liver and brain. Conventional radiation treatment might slow their growth, but Carter was certain to die.
Then his doctors gave him pembrolizumab (Keytruda), a new immunotherapy medication that could spur a patient’s own immune system to attack cancer. Within several months the tumors had melted away. Carter was cured. In fact, he turned 100 just last month.
Today, immunotherapy is the brightest new weapon in the fight against cancer. Miraculous cures, though not experienced by all patients, have become common enough that drugs like Keytruda, Opdivo and Yervoy are known to laypeople and give hope to thousands.
The birth of this dazzling subfield of oncology occurred 40 years ago, when a surgeon at the National Cancer Institute refused to give up on an unproven treatment that had already failed in 66 consecutive patients ‒ all of whom died.
How our immune system could be harnessed to attack cancer
In 1984, Dr. Steven Rosenberg was the chief of surgery at the National Cancer Institute. During his residency training, he had operated on a patient with an extraordinary story. Years before, the patient’s terminal metastatic cancer had been cured after enduring a severe infection accompanied by high fevers. It seemed as if the body’s immune system, galvanized to fight the infection, had somehow also killed the cancer.
But this made little sense. Our immune system is trained to not attack our own cells. Cancer cells originate from our cells ‒ decades of established medical wisdom held that they, too, were invisible to the immune system.
Yet Rosenberg had also encountered another intriguing case ‒ that of an organ transplant recipient who unfortunately received a kidney that was cancerous. The cancer proliferated, until the patient’s immunosuppressive drugs, intended to avert organ rejection, were stopped. At this point, the patient’s revived immune response rejected the donated kidney. Surprisingly, it also eradicated the patient’s cancer.
These patients made Rosenberg wonder whether the immune system could be harnessed to attack cancer. He believed that T cells, the lymphocyte foot soldiers of our immune system, could recognize tumor cells as foreign and kill them, but that there were rarely enough activated T cells to complete the job.
This led Rosenberg to devise a new approach. His plan was to use a cytokine called IL-2, which promotes T cell growth, and use it to supercharge a patient’s T cell activity.
From 1980 to 1984, the surgeon’s efforts failed. He treated 66 patients. None experienced any benefit; all of them died.
“It was not at all clear that our hypothesis was correct,” Rosenberg later wrote of this period. But he didn’t give up.
The 67th patient: Medical file stamped 'death imminent'
His 67th patient was a 33-year-old Navy officer named Linda Taylor. Like former President Carter, she suffered from terminal metastatic melanoma. All her prior treatments had failed, and her medical file had been stamped “death imminent.”
Rosenberg grew billions of Taylor’s T cells in a laboratory. On Nov. 29, 1984, he infused these back into her bloodstream and inoculated her with higher than typical doses of IL-2 repeatedly, hoping to put her immune system into overdrive. The treatment was difficult. Taylor developed fever, chills and pulmonary edema ‒ a result of the body’s intense immune hyperactivity.
“Linda was tough," Rosenberg later recalled. "Not a lot of people could have withstood the treatment.”
“I just sort of took each day at a time,” Taylor recounted in an interview with the National Institutes of Health published in January 2014. “I don’t remember ever wanting to quit.”
About a month later, a biopsy of her tumors showed that the cancer cells were dying. Over the next three months, Taylor’s tumors diminished ‒ and then disappeared.
“For the first time,” Rosenberg wrote, “an immunologic maneuver had caused regression of cancer in a human.”
Taylor returned to the Navy, rose to the rank of captain and later held two command positions in her decades-long career.
Rosenberg treated more patients. In a landmark paper in The New England Journal of Medicine in 1985, his research team reported the achievement of cancer regression in 11 out of 25 cancer patients who had failed all other available treatments.
His success made him a brief medical celebrity. He was featured on the cover of Newsweek and became one of People magazine’s “25 Most Intriguing of 1985.”
In 1992, IL-2 became the first immunotherapy the Food and Drug Administration approved for cancer.
This set the stage for further advances. Today, scientists can engineer T cells with surface receptors that specifically recognize the antigens displayed on the outside of patients’ unique tumor cells. Termed “CAR T-cell therapy,” this is like creating a laser-guided, smart bomb to take out cancer cells with minimal collateral damage.
Immunotherapy drugs are not perfect. They can cause numerous side effects associated with immune hyperactivity, including skin rashes, gastrointestinal problems and hormonal disorders. They aren’t yet effective against many types of cancer, and their cost is often shocking.
Even so, the advent of immunotherapy four decades ago has proved to be a generational breakthrough that has galvanized the depth and breadth of oncology research.
There might never be a magic bullet that will cure all cancers, but the promise of immunotherapy gives us greater confidence that now, more than ever, we can say with conviction that the defeat of cancer will not be a matter of if, but when.
Andrew Lam, MD, is a practicing retina surgeon and an assistant professor at the University of Massachusetts Medical School. He is the author of “Saving Sight” and “The Masters of Medicine: Our Greatest Triumphs in the Race to Cure Humanity’s Deadliest Diseases.”