The hottest topic in conventional cancer research today is immunotherapy. Immunotherapy is a biological therapy that harnesses your own immune system to fight cancer. But the truth is, this form of treatment isn’t all that new.
Doctors have been exploiting the body's innate response against cancer for thousands of years. And these ancient doctors and their treatments have a lot to teach us.
The earliest reference to cancer is attributed to the great Egyptian physician Imhotep, who lived around 2600 BC.
The treatment for tumors, or swellings, as Imhotep wrote, was a poultice followed by an incision. An infection at the tumor site would inevitably follow and provided a rudimentary form of immunotherapy.
The patron saint of cancer patients
In the thirteenth century, the Italian priest Peregrine Laziosi experienced a swelling on his shin. His physician said it was malignant and the only option was to amputate the leg.
But when the lesion grew and broke through the skin, it became severely infected with ‘‘such a horrible stench given off that it could be endured by no one sitting by him.’’
Miraculously, by the time he was due to have his operation no sign of the tumor was found and it never returned. Several centuries later Father Laziosi was canonized and named the patron saint of cancer patients.
By the 18th century, crude forms of immunotherapy became widely known and accepted as an effective treatment for cancer. In fact, medical reports from the time show a regression of any existing tumors whenever the patient came down with an infectious disease of any kind. The list of infections included diphtheria, gonorrhea, hepatitis, influenza, malaria, measles, smallpox, syphilis, and tuberculosis.
In 1844, the visionary French physician StanislasTanchou published a comprehensive treatise on cancer, writing, "One knows that often the affected lymph nodes and primary growths disappear during the course of concurrent illness, never to return. It is according to that idea … that a large number of observers have advised establishing ‘issues’ [pus forming sores] on diverse portions of the body and even in the wounds remaining after operation."
He cites many examples of 'issues' that were established with success.
Doctors of the time used other methods to induce infections including the application of septic dressings to ulcerated tumors or deliberately infecting the patient with bacteria.
For example, in some cases doctors used streptococcus pyogenes to produce a skin rash called erysipelas, as well as bacteria that induced gangrene or syphilis. All three were serious infections that might cure the patients, but also risked killing them.
Early immunotherapy is born
By the late 19th century, doctors developed a systematic approach to applying infections to cancer patients.
It started with Dr. William Coley, a young bone surgeon at New York Memorial Hospital. When Dr. Coley lost his first patient to cancer in 1891, he was so shaken by this failure he set about finding a successful approach.
While searching through hospital records to find other examples of patients with cancer -- an uncommon disease in those days -- he came across a case that was considered hopeless.
The patient had a sarcoma on his neck, and after five operations the wound became infected with erysipelas followed by fever. Yet after each attack the tumor regressed. Eventually it disappeared completely. Seven years later the patient remained cancer-free.
Dr. Coley wrote, "The diagnosis in this case had been repeatedly confirmed by well-known pathologists, and there was no possibility of attributing the cure to any other cause than the erysipelas."
The first case studies of immunotherapy
Dr. Coley looked for other cases in which an infection had cured cancer.
He uncovered 38 reports of cancer patients infected either accidentally or deliberately with erysipelas, which induces fever. In 12 cases of both sarcomas and carcinomas the tumor disappeared completely. In the other 26 cases, patients experienced a substantial improvement.
Seeing such strong evidence to support this approach, Dr. Coley decided to test his theory on a man with inoperable sarcoma of the neck and tonsils whose condition was deemed hopeless. The man was not expected to live for more than a few weeks.
Dr. Coley infected the man with the bacteria that caused erysipelas every three or four days for months, and saw some general improvement in his condition. Still, Dr. Coley grew unsatisfied with the results and with the erysipelas agent available in the U.S., because the man was not growing sick enough, so he obtained a supply from a lab in Germany.
After injecting it directly into the tumor, the patient developed a high fever and rash. Ten days later the patient was much improved, and the neck tumor disappeared two weeks after that. The tonsil tumor regressed but never disappeared completely. The patient rapidly gained strength and remained in remission for another eight years.
Dr. Coley published ten cases of patients treated in this way. In those where a full rash and fever could not be induced, improvement and partial regression was observed. In those experiencing a full erysipelas rash and fever, remission followed. But in two patients the infection raged out of control and killed them.
It was clear to Dr. Coley that a new way of applying the treatment was needed.
Coley's toxins do battle against cancer
Dr. Coley decided to create a vaccine composed of dead strains of bacteria to be certain of inducing a fever, yet do so in a safe way. Dr. Coley still used streptococcus pyogenes, but combined these with the human pathogen serratiamarcescens to increase the virulence of the former bacteria. This vaccine became known as Coley's toxins.
Dr. Coley first used his vaccine on a 16-year-old with an abdominal tumor involving the pelvis and infiltrating the bladder. The teen was in very poor condition, but following treatment his temperature rose by up to six degrees, and after several months the tumor disappeared. The teen lived another 26 years and died from a heart condition at the age of 42.
Coley's toxins became the first recognized immunotherapy for cancer. It received endorsements in New and Nonofficial Remedies of the American Medical Association, and the textbooks Modern Surgery and Modern Operative Surgery.
Dr. Coley’s contemporaries began using it to treat sarcomas, carcinomas, lymphomas, melanomas, and myelomas. They recorded many remarkable recoveries, even in patients in the final stages of the disease.
Doctors also observed marked relief of pain, enhanced wound healing and even bone regeneration.
When Dr. Coley died in 1936, his daughter, Helen Coley-Nauts, continued to promote his work.
She founded the New York Cancer Research Institute with a mission statement of "…understanding the immune system and its relationship to cancer."
Better than existing treatments
In 1953, Helen Coley-Nauts published a detailed analysis of 1200 patients with up to 45 years follow-up who had been treated by her father and other physicians. She reported that 270 patients with inoperable tumors achieved complete regression of their cancers.
"By studying the survival rates following surgery alone and surgery combined with toxins in operable cancer of various types (testis, breast, head and neck, malignant melanoma for example), I found that one could expect from 80 to 100 percent five-year survival in such cases if the toxins were reasonably well administered, as regards to site, dosage frequency, and duration of injections.
"This is a far higher percentage than one can get from the very best surgical procedures, with or without radiation."
Helen Coley-Nauts summarized three important requirements of Coley’s toxins to ensure success. First, the treatment has to induce a fever. Second, the patient must receive regular daily or every-other-day injections directly into the tumor and any metastases (where accessible), for one or two months. Third, a six-month course of weekly injections to prevent recurrence is important to an effective treatment.
The FDA throws up a roadblock
In spite of Helen Coley-Nauts’ efforts, by the time her father died, Coley’s toxins were pushed aside as radiotherapy had become an established treatment and chemotherapy was gaining acceptance. By the early 1960s, a much stronger drug regulatory system was enforced.
As researchers from the University of British Columbia wrote, "After being used for almost 70 years and despite hundreds of publications on its effects on cancer, Coley’s vaccine was assigned ‘‘new drug’’ status in 1963 by the US Food and Drug Administration.
"This ruling forces anyone interested in this area to go through a considerably expensive series of testing protocols that essentially bar Coley’s treatment from being used on cancer patients.
"After this date, the opportunity to develop an inexpensive and effective vaccine for the treatment of a wide spectrum of cancers was virtually lost."
Modern immunotherapy vs. Coley’s toxins
Modern immunotherapy is completely different from Coley’s strategy of inducing a fever to engage the body's innate immune system. Instead, modern immunotherapy targets specific proteins on the cancer cell's surface that can be differentiated from normal cells.
However, Coley's contention that certain microbes can activate the immune system and stall tumor growth when injected into tumors is staging a comeback.
Scientists are experimenting with live copies of the bacterium Clostridium novyi-NT. The bacterium is related to the superbug clostridium difficile but is modified to make it less harmful.
It won't grow in healthy tissue because it only thrives in the low oxygen environment typically found in tumors. The researchers speculate the bacterium releases various enzymes that can break down tumor cells and generates an anti-cancer immune response.
Coley’s toxins in laboratory
and clinical study stops advanced cancer
In 2014, researchers published a paper in the journal Science Translational Medicine in which they described the effect of injecting Clostridium novyi-NT into 16 dogs and one 53-year-old woman with advanced cancer.
In three of the dogs the tumors disappeared, and in another three they shrank. As for the woman, her tumor shrank as well.
With such encouraging results, physicians at the MD Anderson Cancer Center in Houston treated an additional 23 patients suffering from advanced tumors ranging from breast cancer to melanoma and who’d been failed by all other treatments.
Researchers gave a single injection directly at the site of the main tumor. Eleven patients experienced fever, pain and inflammation at the injection site. For 18 of the 23 patients, tumor growth stopped, and metastases stabilized for many.
Lead author Dr. Filip Jankureported,"By exploiting the inherent differences between healthy and cancerous tissue, Clostridium novyi-NT represents a very precise anti-cancer therapeutic that can specifically attack a patient’s cancer.
"From these preliminary results, it appears that Clostridium novyi-NT is able to activate the immune response besides causing tumor destruction.
"We were extremely encouraged by the results of this trial, especially in patients with advanced sarcomas, where immunotherapy hasn’t proven very efficacious."
Another human trial involving 18 patients is currently in progress and is due to end in October 2021.
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