Coley's toxins

Coley's toxins (also called Coley's toxin,

Their use in the late nineteenth and early 20th centuries represented a precursor to modern cancer immunotherapy, although at that time their mechanism of action was not completely understood.^[4]

There is no evidence that Coley's toxins have any effectiveness in treating cancer, and use of them risks causing serious harm.^[5]

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According to Cancer Research UK, "available scientific evidence does not currently support claims that Coley's toxins can treat or prevent cancer".^[5] People with cancer who take Coley's toxins alongside conventional cancer treatments, or who use it as a substitute for those treatments, risk seriously harming their health.^[5]

Bacterial immunotherapy for the treatment of cancer has been utilized throughout history, with the earliest cases going back to c. 2600 BC.^[6] Egyptian physician Imhotep treated tumors by a poultice, followed by incision, to facilitate the development of infection in the desired location and cause regression of the tumors. In 13th century, St. Peregrine experienced spontaneous regression of tumor, after the tumor became infected. In the 18th and 19th centuries, deliberate infection of tumors was a standard treatment, whereby surgical wounds were left open to facilitate the development of infection. Throughout the time period, physicians reported successful treatment of cancer by exposing the tumor to infection including the report of French physician Dussosoy who covered an ulcerated breast carcinoma with gangrenous discharge soaked cloth, resulting in disappearance of tumor.^[7][8][9] Observations of a relationship between infection and cancer regression date back to at least the 18th century.^[10][11] More specifically, observations of an apparent relationship between erysipelas and remission of cancer predate Coley.^[12] For example, Anton Chekhov, in his capacity as a physician, recorded such a relationship in 1884.^[13]

Coley started his investigations after the death of one of his first patients, Elizabeth Dashiell, from sarcoma. Dashiell was a close childhood friend of John D. Rockefeller Jr., who later indicated that her death was what first motivated his subsequent funding of cancer research.^[14][4]

Frustrated by this case, Coley's subsequent research led him to announce evidence of the apparent relationship between infection and cancer regression, which he published in 1891.^[15] His initial attempts at deliberate infection were mixed,^[16] but in 1893 he began combining Streptococcus pyogenes and Serratia marcescens, based upon research from G.H. Roger indicating that this combination led to greater virulence.^[17]

Coley published the results of his work as a case series, making it difficult to interpret them with confidence. According to the American Cancer Society, "more research would be needed to determine what benefit, if any, this therapy might have for people with cancer".^[18]

The so-called Coley's toxins were used against different types of cancer from the year 1893^[19] through the year 1963. Within the preparation's first decade, it was changed from an unfiltered mixture of killed bacteria to a porcelain-filtered mixture,^[4] which reduced the adverse effect profile.^[4] From 1923 on, Parke-Davis was the only commercial source of Coley's toxins in the United States. Hall (1997)^[4] explains that the versions used by Coley himself were custom-compounded, although the formula for the preparation was never standardized.^[20]

In the wake of the

Coley's toxins were also produced by the small German pharmaceutical company Südmedica[23] and sold under the trade name Vaccineurin.^[24] However, production ceased by 1990 because of a lack of re-approval by German Federal Institute for Drugs and Medical Devices.

There were multiple rationales proposed for how Coley's toxins might work.

One rationale argues that macrophages are either in "repair mode", furthering the growing of cancer, or in "defense mode", destroying cancer. However, macrophages are in "defense mode" only if there is some recognized enemy. As cancer tissue is not recognized as enemy (but as normal body tissue), there is a need to bring more macrophages into "defense mode" by simulating an infection. The simulated infection results in a real fever. Unlike hyperthermia, real fever not only means heating of the body but also higher activity of the immune system. Thus, fever is seen as a precondition for a therapy using Coley's Toxins to succeed.^[10][25][26]

One of the agents in Coley's Toxin that is thought to be biologically active is a

A robust fever, which occurs in response to Coley fluid, generates inflammatory factors with co-stimulatory activity, which activate resting dendritic cells (DC), leading to the activation of anergic T cells, possibly accomplished through a second process, where physical damage to cancer cells leads to a sudden supply of cancer antigens to the dendritic cell population.^[10][25]

A private biotech company, Coley Pharmaceutical Group, has conducted clinical trials using genetic sequences which may have contributed to Coley's toxin's effectiveness, and was acquired by Pfizer in January 2008.^[32] In addition, the Waisbren Clinic in Wisconsin reports they have used Coley's toxin to treat patients since 1972.^[33] Coley's toxins are generally not available where approval or licence is required (in particular in the United States and Germany).

Drug makers including

• Immunotherapy
• Cancer immunotherapy
• Cancer vaccine
• List of unproven and disproven cancer treatments