Immunotherapy: Revolutionizing Cancer Treatment since 1891

By Matthew Tontonoz,

Monday, December 28, 2015


Immunotherapy’s long and distinguished tradition at Memorial Sloan Kettering goes all the way back to William Coley, now considered the “Father of Cancer Immunotherapy.” His work paved the way for the modern immunotherapies that are helping patients today.   

  • Immunotherapy as an approach to cancer treatment got its start more than 100 years ago.
  • William Coley, an MSK-affiliated surgeon, developed an early form of immunotherapy using bacterial toxins.
  • Inspired by Dr. Coley’s method, other MSK scientists studied the relationship between the immune system and cancer.

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. 

Nature often gives us hints to her profoundest secrets.
William Coley MSK surgeon and immunotherapy pioneer
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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?

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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. 

Experts today agree that Dr. Coley’s toxins likely benefited many patients who received them.

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.

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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.  

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.

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 and Immunotherapeutics Service and holder of the Lloyd J. Old Chair for Clinical Investigation at MSK.

I'm really proud and privileged to be in the lineage of descendants from Coley.
Jedd Wolchok
Jedd Wolchok MSK cancer immunologist

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.

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In my new book Smart Decisions about Breast Cancer (a health literacy book), my research chapter addresses Dr Coley's contribution using his Mixed Bacterial Vaccine (MBV) and I postulate that some new vaccines using disabled viruses is a variant of Dr Coley's MBV. Can you elaborate on why Coley's MBV was phased out to make room for the "modern day" chemotherapy drugs?
Thank you,
Martina Wood, Author

Dear Martina, we forwarded your question to Dr. Wolchok and he responded:

"Great comment and we agree that the current viral therapies can certainly trace a lineage to Coley's Toxins. The absence of detailed mechanistic understanding of Coley's Toxins for almost a century, combined with the development of radiation therapy and then chemotherapy likely contributed to the waning of use of Coley's Toxins during the first half of the 20th century."

Thank you for your comment.

Any hope for immunotherapy in treating metastatic breast cancer?

Dear Janet, immunotherapy is currently being studied as a treatment for people with advanced breast cancer in clinical trials. Here is a listing of several such trials currently enrolling patients at MSK:…

If you have any questions about these or other clinical studies at MSK or would like to make an appointment to determine whether this may be a treatment option for you, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

My husband had an aggressive form of bladder cancer. Two surgeries and a three-year treatment plan with BCG saved his life. The urologist would beam at the effectiveness of this treatment. We are eternally grateful for that drug and this research. I've read about Dr. Donald Lamm in Arizona, formerly from NYC, who fought hard to have BCG made available for treatment. Thank you to all the dedicated researchers involved in immunotherapy.

Is anyone doing any clinical trials on adenoid cystic carcinoma? My wife has been fighting this relentless cancer for 30 years with surgeries and she has pretty much depleted her options for more invasive treatments!

Dear Dean, we are sorry to hear about your wife's long-time struggle with adenoid cystic carcinoma. It has been an active area of research at MSK and elsewhere. Some of the latest research advances are summarized in this 2013 blog post:….

You may also be interested in taking a look at some of our clinical trials for head and neck cancer, which are listed here: Here is one listed specifically for people with ACC:

If you have additional questions about our trials or would like to make an appointment for your wife to meet with one of our specialists to discuss possible treatment options, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

My cousin is currently fighting metastatic bladder cancer by participating in a trial of a PD1 inhibitor drug. So far, the results seem positive, but I am interested in more Information about BCG. Can you steer me in the right direction? Also, are trials being done at Memorial hospital using BCG for advanced bladder cancer?

Dear Lisa, we are sorry to hear about your cousin's diagnosis. We are not currently conducting any trials investigating BCG for people with advanced bladder cancer. If you are interested in browsing through the trials we do have open for people with bladder cancer, please visit If your cousin has any questions about these trials or would like to make an appointment, please ask him or her to call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

Where are we in clinical trials with sarcomas and immune therapy? I was diagnosed October 2014 with one of the rarest firms of soft tissue sarcoma called alveolar soft part sarcoma. Understanding my subtype affects approx 80-100 patients a year. As I have read the Coley story sometime back and how interesting he was dealing with sarcoma, are you having any success with any of the subtypes? Sarcoma is not a household cancer name so you hear much about other cancers and advancement in clinical trials and immune response but what about rare cancers like sarcoma and all the different subtypes? Thank you for your time.

Kristi, Memorial Sloan Kettering has ongoing trials looking at immunotherapy for various types of sarcoma, and will begin enrolling patients in more trials soon. If you'd like to learn about participating in one of them, you can call our Physician Referral Service at 800-525-2225 or go to for more information on making an appointment.

In addition, you may be interested in reading about the work of one of our medical oncologists, Sandra D'Angelo, to develop immunotherapy for sarcoma:

Thank you for your comment.

I am wonderful about 4th stage Ovarian Cancer and immunotherapy treatment. Has there been any success with this therapy? Trials?

Dear Lesley, we are actively investigating immune therapies for the treatment of people with ovarian cancer. These trials are listed here, along with clinical studies evaluating other treatments for women with this disease: If you have questions about any of these trials or would like to make an appointment, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

My mother was just diagnosed with pancreatic cancer, stage 4. The main tumor itself is not that large. Is there anything in the immunotherapy area that might help her?

Dear David, we are sorry to hear about your mother's diagnosis. We are actively investigating the use of immunotherapy and other treatments for people with pancreatic cancer. Those clinical trials are listed here: If you have questions about any of these studies or would like to make an appointment for your mother, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

Is immunotherapy something that can be used for esophageal cancer?

Dear Jane, we are currently investigating immunotherapy, as well as other new treatments, for people with esophageal cancer. You may browse through these studies here: If you have any questions about these clinical trials or would like to make an appointment with one of our specialists to discuss possible treatment options, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

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