Can Immune Therapy Fight Cancer?
Can the body’s immune response help treat cancer?
In recent years, researchers have looked at how to stimulate T-cells to combat tumors.
In the summer of 1890, an adventurous seventeen-year-old from New Jersey named Elizabeth Dashiell travelled across the United States by train. During the journey, she caught her hand between the seats of a Pullman car. The hand became swollen and painful, and, when it didn’t heal after she returned home, Dashiell consulted William Coley, a young surgeon in New York City. Unable to determine a diagnosis, he made a small incision below the bottom joint of her pinkie finger, where it connected to the back of her hand, to relieve the pressure, but only a few drops of pus drained out. During the following weeks, Coley saw Dashiell regularly. In the operating room, he scraped hard, gristly material off the bones of her hand. But the procedure gave only fleeting relief. Finally, Coley performed a biopsy that showed that Dashiell had sarcoma, a cancer of the connective tissue, which was unrelated to her initial injury. In a desperate attempt to stop the cancer’s spread, Coley followed the practice of the time and amputated Dashiell’s arm just below the elbow. But the sarcoma soon reappeared, as large masses in her neck and abdomen. In January, 1891, she died at home, with Coley at her bedside.
After Dashiell’s death, Coley was distraught, and searched through the records of New York Hospital for similar cases. He found one patient who stood out from the grim stories. Eleven years earlier, Fred Stein, a German immigrant who worked as a housepainter, had a rapidly growing sarcoma in his neck. After four operations and four recurrences of the cancer, a senior surgeon declared Stein’s case “absolutely hopeless.” Then an infection caused by streptococcal bacteria broke out in red patches across Stein’s neck and face. There were no antibiotics at the time, so his immune system was left to fight off the infection unaided. Remarkably, as his white blood cells combatted the bacteria, the sarcoma shrank into a bland scar. Stein left the hospital with no infection and no discernible cancer. Coley concluded that something in Stein’s own body had shrunk the cancer.
Coley spent the next decade hoping to replicate Stein’s extraordinary recovery. In “A Commotion in the Blood,” published in 1997, Stephen S. Hall describes how Coley inoculated cancer patients, first with extracts of streptococcal abscesses, termed “laudable pus,” and later with purer cultures of the microbes. He claimed several successes, but the medical establishment did not embrace his approach, because his results could not be reliably reproduced. His primary critic, the pathologist James Ewing, believed that the new technique of radiation was the only scientifically sound way to treat cancer.
Coley’s work was financially supported by John D. Rockefeller, Jr., a classmate of Dashiell’s brother who had considered Elizabeth his “adopted sister.” But Rockefeller also donated to Ewing’s research. While Coley told stories of miraculous recoveries, Ewing presented numbers that consistently demonstrated the power of radiation. Ultimately, Rockefeller chose Ewing as his scientific adviser. Rockefeller’s support led to the creation of what is now the Memorial Sloan-Kettering Cancer Center, one of the foremost institutions studying and treating malignancies. The idea that the body’s immune system could play a crucial role in eradicating cancer was largely discarded. One doctor at the time called Coley’s hypothesis “whispers of nature.”
In the last hundred years, progress in the treatment of cancer has come mostly from radiation and chemotherapy. Previously fatal blood-cell cancers, such as childhood leukemia and Hodgkin’s disease, are now curable. But solid tumors, which grow in the lungs, the colon, and the breast, have stubbornly resisted treatment once they spread beyond their initial site.
In 1971, the Nixon Administration declared a “war on cancer,” promising Americans that within ten years the disease would be beaten. At the time, many researchers believed that cancer was caused by a virus that speeded up a cell’s metabolism, resulting in uncontrollable growth. After all, they had discovered some hundred viruses that caused cancer in amphibians, birds, and mammals. In the early seventies, interferon, a drug that had been developed from a protein released by white blood cells during a viral infection, was widely thought to be a possible cure for cancer; in 1980, it appeared on the cover of Time. The tumors of mice shrank dramatically when treated with the drug. But in patients interferon failed to cure solid tumors, and melanoma responded only occasionally.
Over the next decade, other proteins produced by the body as part of its immune response were made into drugs, most notably one called interleukin-2. In 1988, Armand Hammer, the ninety-year-old oil-company magnate who chaired Ronald Reagan’s cancer panel, sought to raise a billion dollars, with the aim of curing cancer by his hundredth birthday. He touted interleukin-2 as an immune booster that could achieve the goal. But most solid tumors were impervious to it, too.
In the past fifteen years, as tumors have been found to contain genetic mutations that cause them to grow unrestrained, the focus of research has shifted to cancer’s genome. Targeted therapies, which are designed to disarm these mutations, are now at the forefront of care. The first successful targeted therapy was Gleevec, which caused rapid remissions in chronic myelogenous leukemia, with few and mild side effects. Herceptin, a targeted therapy that attacks HER-2, a protein that is found in some twenty to thirty per cent of breast-cancer cases, has also been effective.
Advances such as these caused Coley’s approach to fade into obscurity. Harold Varmus, a Nobel laureate and the director of the National Cancer Institute, told me that until very recently, “except for monoclonal antibodies, every therapy that exploited the immune system was pretty abysmal. There weren’t any good ideas about why immune therapy failed.” But now patients who did not respond to available therapies have shown dramatic and unexpected responses to a new series of treatments that unleash the immune system. Coley’s theories are suddenly the basis for the most promising directions in cancer research. In March, 2011, the National Cancer Institute announced that it would fund a network of twenty-seven universities and cancer centers across North America to conduct trials of immune therapies. Mac Cheever, the director of the program, who is at the Fred Hutchinson Cancer Research Center, in Seattle, described it as a way to speed the practical work of developing treatments. “All of the components needed for effective immunotherapy have been invented,” he said.
Posted on May 8, 2013, in Government, Health, SCIENCE and tagged Coley, Fred Hutchinson Cancer Research Center, Fred Stein, National Cancer Institute, New York City, Ronald Reagan, United States, William Coley. Bookmark the permalink. Leave a comment.