Immunotherapies, treatments that harness the power of our own immune system to fight disease, are becoming a core part of cancer care. Just this past year, the US Food and Drug Administration approved new immunotherapies for the treatment of melanoma, lung cancer, and kidney cancer.
Drugs such as checkpoint inhibitors, which “release the brakes” on the immune system, and cell-based therapies using genetically engineered immune cells are producing stunning results in some patients, effectively curing them of their cancer.
What many people might not realize is that immunotherapy is more than a century old — it was in fact the first nonsurgical treatment for cancer — and it was born at Memorial Sloan Kettering.
From Tragedy to Breakthrough
It all goes back to the experience of a young woman named Elizabeth “Bessie” Dashiell. While traveling on a train car in the summer of 1890, Bessie hurt her hand. In the weeks that followed, a lump developed, followed by nagging pain.
She went to see William Coley, a 28-year-old doctor just out of his surgical residency and practicing in New York City. Dr. Coley performed a biopsy of the hand, expecting to find evidence of infection or inflammation. Instead, he found something much worse: an aggressive bone cancer called sarcoma.
Dr. Coley did the best he could for his young patient — which at the time meant amputating her arm below the elbow — but the cancer spread mercilessly through her body. Bessie died in January 1891 at the age of 18.
Bessie’s tragic death affected Dr. Coley deeply. It inspired him to search for better ways to treat cancer and set him on a path that ultimately led to a breakthrough in cancer treatment.
Hunting Down a Cure
Hoping to find a better way of treating the cancer that took Bessie’s life, Dr. Coley pored through 15 years’ worth of hospital case files to see how other doctors had handled sarcoma. One case jumped out at him: a 31-year-old man whose sarcoma had apparently regressed completely after he came down with a postoperative skin infection called erysipelas (caused by strep bacteria). His curiosity piqued, Dr. Coley went in search of the man and eventually found him in the tenements on New York City’s Lower East Side, still alive and cancer free seven years later.
Struggling to make sense of this oddity, Dr. Coley combed the medical literature and discovered other reported cases of cancers that had “spontaneously regressed” following an infection.
This gave him an idea: If accidental infections sometimes caused cancer to regress, why not intentionally produce an infection to treat the disease?
Dr. Coley tried this unorthodox approach on a 35-year-old man with a terminal case of neck cancer, injecting his tumor with the erysipelas germ. To Dr. Coley’s great delight, the gambit paid off. The man’s cancer regressed completely and he lived for another eight years.
“Nature often gives us hints to her profoundest secrets,” Dr. Coley mused in 1891 on the curious findings that set him down this path.
He experimented with this approach for the rest of his career, much of it spent as head of the bone tumor service at Memorial Hospital. Eventually he switched from using living bacteria — which could be quite dangerous — to using heated-killed bacteria, a concoction that became known as Coley’s toxins.
Experts today agree that Coley’s toxins likely benefited many patients who received them. So why did they fall out of use?Back to top
Waiting for Science to Catch Up
Dr. Coley had the misfortune of working at time when little was known about the immune system. No one, not even Dr. Coley, had a good explanation of how the toxins worked. What’s more, he was developing his technique right around the time that radiation was coming into use as a cancer treatment. Unlike his toxins, which worked only sporadically and mysteriously, radiation therapy achieved objective tumor reductions in nearly every patient; the dramatic effects of radiation served to sideline Dr. Coley’s less-predictable method among cancer doctors.
A few dedicated souls stuck with it, however. One was Dr. Coley’s son Bradley, who succeeded him as head of the bone tumor service at MSK. Bradley treated many patients with the toxins in the 1940s and 1950s, including some who are still alive today. But the toxins were hard to administer and not easily standardized, leading to lingering questions about their efficacy.
By this time, another important approach to cancer treatment was rising to prominence: chemotherapy. Like radiation before it, chemotherapy had powerful and predictable effects, and it further eclipsed alternative approaches. By the time Bradley retired in the 1950s, Coley’s toxins were no longer being used to treat patients at MSK.Back to top
Rekindling Interest in an Old Approach
Dr. Coley’s novel approach to cancer treatment might have fallen completely into historical obscurity were it not for the efforts of his daughter, Helen Coley Nauts. After her father’s death, in 1936, she studied his case files and became convinced his method had achieved remarkable results and should be studied further. But Mrs. Nauts lacked medical credentials, and many in the wider profession dismissed her.
One person who paid attention, though, was Lloyd Old, a rising star in immunology who joined MSK in 1958 and served as its Director of Research from 1973 to 1983. Dr. Old was impressed by Mrs. Nauts’s reevaluations of her father’s work and vowed to study the Coley phenomenon further.
Having a well-respected scientist on her side greatly aided Mrs. Nauts’s efforts to garner support for research into the immune system and cancer. The organization she founded, the Cancer Research Institute, still exists today. Dr. Old, who died in 2011, was its scientific director for 40 years.
Dr. Old did some of the first modern research on immunotherapy, with a substance called BCG, now an FDA-approved treatment for bladder cancer. BCG is made from a weakened version of the bacterium that causes tuberculosis. Experts think Coley’s toxins may have worked in a similar manner to BCG — jumpstarting an immune response to cancer by provoking one against the bacteria.
Dr. Old impacted cancer immunotherapy in yet another important way: by serving as teacher and mentor to many future leaders in the field. One of those students was Jedd Wolchok, now Chief of the Melanoma Service and holder of the Lloyd J. Old Chair for Clinical Investigation at MSK.
Dr. Wolchok has played a central role in developing new immunotherapy treatments for melanoma, including the immune checkpoint inhibitors ipilimumab and nivolumab, which have revolutionized treatment for this disease.
Reflecting on the long, sometimes-uphill road to medical acceptance, Dr. Wolchok said, “I’m really proud and privileged to be in the lineage of descendants from Coley who have contributed to the field of immunotherapy at MSK. It’s exciting to be at one of the places where immunotherapy got started.”
“It’s especially gratifying now that we have medicines that are truly impactful and are helping patients with a broad spectrum of cancers,” he added.
Hear more about the early history of immunotherapy on NPR’s Morning Edition, featuring an interview with Stephen Hall, author of the book “A Commotion in the Blood,” which recounts much of this history.Back to top