Is immunotherapy the key to curing cancer?

01 Jan 2019

Is immunotherapy the key to curing cancer?

 

The medical profession at last seem to be awakening to the possibility that by using the body's own immune system one can unlock the key to a potential cure for a wide range of advanced and/or inoperable cancers. Yet this technology has been known and demonstrated for over a hundred years. Why has no one listened?

 

In 1891 Dr. William Coley, a young surgeon at the Memorial Sloan-Kettering Cancer Centre in New York  became the first physician to cure cancer with a non-surgical therapy. Perhaps even more remarkably, he was the first physician to cure any disease with an immune therapy when he injected live bacteria into a young man with an inoperable sarcoma.

 

Chance encounter

 

This “treatment”, like many great discoveries, came about almost by accident. One of Coley’s first patients presented with an egg-sized sarcoma on his left cheek. The sarcoma was operated on twice but recurred. The extensive wound after surgery could not be closed and skin grafts were unsuccessful. Ironically, this failure to close the wound was to play a crucial role in the patient’s eventual recovery.

 

The tumour progressed and a final operation only partially removed the growth. His case was considered hopeless. However, after the last operation, the wound became infected and the patient developed a high fever.  The infective agent was shown to be Streptococcus pyogenes or erysipelas as it was known at the time.

 

Little could be done to stop the infection, yet surprisingly, after each attack of fever, the ulcer improved, the tumour shrank and finally disappeared completely and the patient was fully discharged some 4.5 months later.

 

Tumour rumours

 

During his investigations, Coley discovered a common theme. For hundreds of years, doctors had reported many cases where tumours had disappeared, apparently spontaneously. He researched more and more cases of spontaneous regression involving cancer patients and found that many of these people had something in common apart from their miraculous recovery.

 

Most had been struck down by an acute infectious disease. It might have been flu or measles, malaria, smallpox or syphilis; or like one of Coley’s first patients, erysipelas. In most cases, their fever subsided, their tumours had broken down and been absorbed or sloughed off. Indeed, infection coupled with a febrile response by the patient seemed to be the key to many of the “cures.”

 

It is worth noting that fever is a highly conserved physiological response to infectious stimuli. It is more than just a rise in body temperature and not analogous to hyperthermia (that is a mechanically achieved increase in temperature). Febrile thermogenesis (e.g. chill, shivering etc.) is associated with an increase in metabolic rate of 2-3 times, while maintenance of a fever has been associated with a 30-50% increase in metabolic rate. It is unlikely that such a response would be conserved unless it had considerable use or adaptive value.

 

Super soup

 

After years of experimentation, Coley produced a heat killed mixed culture of two  bacteria which subsequently became known as Coley’s vaccine or Coley’s toxins. These toxins were, in effect, a crude “soup” of culture medium, bacterial cells, bacterial metabolites and cell debris.

After Coley’s vaccine is administered, a wide range of cytokines become detectable in the urine including Interleukins 1,2, 6, 8, 10, 12 and 18; gamma-interferon, protein 10, macrophage stimulating factor and TNF.

 

Many more cytokines are upregulated and others down regulated to varying degrees throughout the course of treatment, yet, this illustrates the point that individual immumodulating cytokines are in fact only a small facet of this complex immunological response to infection, and correspondingly, tumour regression.

 

That said, there are undoubtedly  key cytokines at play as part of the immune response to Coley’s vaccine; principally Interleukin 2 which is produced by Th1 cells (Th1 being a specific group of lymphocytes or specialised white blood cell often referred to as T helper cells which play an important role in all immune responses). In particular, they help activate and direct other cells within the immune system such as cytotoxic T cells and macrophages. It was almost as if the very high fever or “crisis” induced by Coley’s toxins produced a greatly enhanced response from the body’s immune system. One which in addition to attacking the bacterial inocula, also attacked and destroyed the tumour cells.

 

Fever pitch

 

It is now widely accepted that the immune system works at its best during a fever. In 1950, Dr M.J. Shear, an oncologist at the Children’s Hospital in Boston, examined a large series of children with untreated acute leukaemia. In those that experienced spontaneous remissions, three quarters of these remissions were preceded by acute infections. He made the following comment:

 

Are pathogenic and non-pathogenic micro-organisms one of nature’s controls of microscopic foci of malignant tissue, and, in making progress in the control of infectious disease, are we removing one of nature’s controls of cancer?”

 

During Coleys career he treated around 1000 cases  many of which featured advanced or metastatic cancers with around 20% resulting in total regression of the disease. After his death, and in the intervening years, several other groups of workers have tried to replicate Coleys work with mixed results.

 

Slow burn

Despite numerous long-term successes especially in Coley’s and his colleagues hands, the vaccine was a disappointment in the hands of many physicians. The reason was related to difficulties in vaccine manufacture This disenchantment occurred at the same time as radiotherapy was seen as a much more effective and easier therapy to provide than Coley’s, but time would tell a different story.

 

In 2005 a Canadian company, MBVax Bioscience, developed and produced Coley Fluid, a modern formulation of Coley’s Toxins, and provided it free of charge to physicians anywhere in the world who could legally import the product and administer treatment. The limited clinical results thus far clearly demonstrate Coley Fluid can induce complete durable regressions of cancers no longer responsive to conventional therapies.

 

MBVax clinical results in patients receiving Coley Fluid as a single agent included durable complete responses of metastatic breast cancer, lung cancer, esophageal cancer, stomach cancer, lymphoma and melanoma. (The term “long-term cure” is equivalent to a durable complete response, meaning at the end of therapy there remains no detectable cancer and the absence of cancer persists for at least one year).

 

Trial and error

 

However, despite these results and the support of leading cancer researchers; regulatory bodies in Canada, Europe and the U.S. denied permission to commence more comprehensive clinical trials. This resulted in the complete cessation of work by MBVax.

 

To help ensure that the technology to develop Coley’s toxins is not lost to the scientific community, Don MacAdam, former CEO of MBVax has written a *book 'The Reinvention of Coley’s Toxins' which tells the story of MBVax Bioscience and provides valuable historical information, specifically to ensure the correct formulation is not once again forgotten.

 

More than that, this book is the story of how a small company with limited finances managed to manufacture Coley’s toxins in a similar manner to the most effective vaccine types produced during Coley’s time, despite all the odds being against it. It is a story of the passion of a few men, the struggles of finance and investment and the fight against regulatory authorities that made it impossible for a small company to succeed.

 

MacAdam may have lost this battle but he has not lost the war. The  final chapters of the book are a gift to doctors and scientists of the future. He has provided in great detail how to produce Coley’s toxins according to the original manufacturing process and it is now up to others to take up the baton and return this therapy to its rightful place.

 

Peter Green

 

The Reinvention of Coley’s Toxins

Donald H. MacAdam

278 pages, illustrated, color, about $19.95 (US)

Publisher: www.volumesdirect.com/detail.aspx?ID=5544

Amazon: https://amzn.to/2xeY4LD