94:
473:
challenge or modulation are not specific enough (not targeted enough), present too many harms, and do not work consistently enough to bring benefits to most patients, being dependent on idiotypic molecular factors (which were not understood at all when the therapies were first developed and which even today are still not easy for immunotherapy designers to deal with).
291:
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
463:
and
William Coley as colleagues at the same institution. Hall explains that the aspects of Coley's work that were scientifically underpowered—the anecdotal emphasis, the lack of a standardized formula for the toxins preparations, the lack of methodologically rigorous clinical trials, and (relatedly)
228:
The so-called Coley's toxins were used against different types of cancer from the year 1893 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, which reduced the adverse effect profile. From 1923
182:
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
472:
as alternative medicine is flawed, given what humanity now knows about molecular biology that was not known when these older therapies were tried: Even if certain kinds of immune challenge or immunomodulation can produce desirable immunotherapeutic effects, these crude methods of inducing such
459:, Coley's toxins were opposed by the medical establishment despite his reports of good results, because his reports were not believed to be credible. Hall (1997) extensively explores the issue; one of the lenses through which Hall explores it is the decades-long, complicated relationship of
173:
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
464:
the problem of poor replicability—led many scientists to dismiss all use of Coley's toxins as mere hogwash. Although the truth was more complex than that dismissal recognized, it is a fact that the toxins never made it to the stage of a safe and effective medication, and today their use as
150:, "available scientific evidence does not currently support claims that Coley's toxins can treat or prevent cancer". 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.
205:
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. His initial attempts at deliberate infection were mixed, but in 1893 he began combining
642:
405:
Some specialized medical doctors in
Germany apply Coley's toxins to patients. They can do so legally because, in Germany, unapproved medications may be produced, although they may not be sold or given away. Physicians can go to special
183:
soaked cloth, resulting in disappearance of tumor. Observations of a relationship between infection and cancer regression date back to at least the 18th century. More specifically, observations of an apparent relationship between
1603:
1010:
370:(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.
650:
378:
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
1600:
1018:
354:
from the patient) is the active agent of Coley's toxins. This hypothesis is supported by the fact that streptokinase has been associated with successful treatment of
436:
237:. Hall (1997) explains that the versions used by Coley himself were custom-compounded, although the formula for the preparation was never standardized.
1039:
Coley WB. The treatment of malignant tumors by repeated inoculations of
Erysipelas, with a report of ten original cases. Am J Med Sci 1893;105:487–511.
410:
and produce Coley's toxins there using their own hands. Coley's toxins may still be applied by a licensed medical doctor, because in
Germany there is "
497:
420:"), the legal right to apply whichever therapy a physician considers to be appropriate in the light of their medical knowledge. For example, Dr
268:
424:
used several unconventional and controversial treatments, including Coley's toxins, for cancer patients in the second half of the 20th century.
1459:
559:
Taniguchi Y, Nishizawa T, Kouhchi C, et al. (2006). "Identification and characterization of lipopolysaccharide in acetic acid bacteria".
366:
A robust fever, which occurs in response to Coley fluid, generates inflammatory factors with co-stimulatory activity, which activate resting
1163:
836:
1383:
Hussein EA, el Dorri A (1993). "Intra-arterial streptokinase as adjuvant therapy for complicated
Buerger's disease: early trials".
382:
in
January 2008. In addition, the Waisbren Clinic in Wisconsin reports they have used Coley's toxin to treat patients since 1972.
221:
Coley published the results of his work as a case series, making it difficult to interpret them with confidence. According to the
1411:
80:
There is no evidence that Coley's toxins have any effectiveness in treating cancer, and use of them risks causing serious harm.
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which causes fever. The resulting fever from the lipopolysaccharide is thought to increase lymphocyte activity and boosts
1483:
397:
are interested in modern versions of Coley's toxins; Pfizer has acquired the Coley
Pharmaceutical Group, set up in 1997
1121:
621:
225:, "more research would be needed to determine what benefit, if any, this therapy might have for people with cancer".
133:
386:
are generally not available where approval or licence is required (in particular in the United States and
Germany).
587:
Pick, Thomas Pickering, "Surgery," Longmans, Green and Company, 1899, Pages 250–251. Retrieved August 3, 2010.
681:"Spontaneous regression of tumour and the role of microbial infection – possibilities for cancer treatment"
249:
63:
1588:
664:
Cann; et al. (2003). "Dr William Coley and tumour regression: A place in history or in the future".
321:
202:, who later indicated that her death was what first motivated his subsequent funding of cancer research.
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194:
Coley started his investigations after the death of one of his first patients, Elizabeth Dashiell, from
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for the treatment of cancer has been utilized throughout history, with the earliest cases going back to
111:
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1137:
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355:
115:
104:
516:
Thotathil Z, Jameson MB (2007). "Early experience with novel immunomodulators for cancer treatment".
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245:
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222:
218:, based upon research from G.H. Roger indicating that this combination led to greater virulence.
199:
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346:
208:
44:
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1070:"Coley's Toxins – The First Century Townsend Letter for Doctors and Patients – Find Articles"
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73:
Their use in the late nineteenth and early 20th centuries represented a precursor to modern
487:
465:
440:
74:
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is not the same type of treatment, although sometimes incorrectly called "fever therapy".
8:
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50:
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308:. Thus, fever is seen as a precondition for a therapy using Coley's Toxins to succeed.
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1293:"Coley's toxin revisited: immunotherapy or plasminogen activator therapy of cancer?"
545:
256:. Since then, several small clinical trials have been conducted with mixed results.
1535:
1524:"The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas"
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962:"The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas"
901:
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One of the agents in Coley's Toxin that is thought to be biologically active is a
1607:
1269:
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840:
696:
417:
77:, although at that time their mechanism of action was not completely understood.
1471:
news-medical.net: Pfizer to acquire Coley Pharmaceutical Group, 19 November 2007
1460:
New York Times: article on Pfizer and Coley Pharmaceutical Group, 5 October 2005
905:
304:, real fever not only means heating of the body but also higher activity of the
267:. However, production ceased by 1990 because of a lack of re-approval by German
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329:
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Bacterial toxins formerly used in a precursor analogue of modern immunotherapy
1620:
1186:"Dr William Coley and tumour regression: a place in history or in the future"
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Coley's toxins were also produced by the small German pharmaceutical company
234:
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55:
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781:"Fever in Cancer Treatment: Coley's Therapy and Epidemiologic Observations"
765:
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There were multiple rationales proposed for how Coley's toxins might work.
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42:) is a mixture containing toxins filtered from killed bacteria of species
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241:
230:
191:, in his capacity as a physician, recorded such a relationship in 1884.
288:
184:
1114:
Can bacteria cause cancer?: alternative medicine confronts big science
66:
who developed the mixture in the late 19th century as a treatment for
882:
W. Busch. Einfluβ von Erysipel. Berliner Klin Wschr 1866. 3: 245–246.
293:
175:
847:, Cancer Immunol Immunother 2001) 50: 391–396 10.1007/s002620100216
170:
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1183:
730:"Immunity over inability: The spontaneous regression of cancer"
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of 1962, Coley's toxins were assigned "new drug" status by the
67:
297:
612:
A commotion in the blood: life, death, and the immune system
1155:
1153:
1000:
Roger, G.H. Séances et Mém Soc de Biol Paris 1890;2:573–580
892:
Gresser I (1987). "A. Chekhov, M.D., and Coley's toxins".
1256:
Tsung K, Norton JA (2006). "Lessons from Coley's Toxin".
558:
1150:
678:
311:
233:
was the only commercial source of Coley's toxins in the
1102:, published February 18, 2008. Accessed March 26, 2008.
252:(FDA), making it illegal to prescribe them outside of
114:. Please help to ensure that disputed statements are
187:
and remission of cancer predate Coley. For example,
1184:Hoption Cann S, van Netten J, van Netten C (2003).
1116:. New York: New York University Press. p. 11.
603:
601:
599:
597:
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439:). This term was introduced by E. Göhring in 1985.
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328:reported that the active agent was thought to be
1618:
1174:, British Journal of Cancer (2005) 92, 421 – 425
607:
590:
515:
498:List of unproven and disproven cancer treatments
1573:, William B. Coley, Surgeon-in-Chief, 1925-1933
1382:
269:Federal Institute for Drugs and Medical Devices
1111:
643:"What is Coley's toxins treatment for cancer?"
1403:
1333:
953:
857:Kleef, Ralf; Hager, E. Dieter (2006-09-15).
296:. The simulated infection results in a real
178:of tumors was a standard treatment, whereby
1376:
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959:
950:Coley WB. Annals of Surgery 1891;14:199–200
885:
552:
509:
468:is clearly flawed for the same reason that
198:. Dashiell was a close childhood friend of
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826:
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1484:"Fiebertherapie bei Krebs vernachlässigt"
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134:Learn how and when to remove this message
1521:
1074:Townsend Letter for Doctors and Patients
450:
344:(produced by killed bacteria of species
110:Relevant discussion may be found on the
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1475:
1409:
1340:Haux J (2001). "Infection and cancer".
821:
727:
518:Expert Opinion on Investigational Drugs
1619:
1339:
637:
635:
633:
1594:
1412:"Cancer and the bacterial connection"
435:) or better "Aktive Fiebertherapie" (
312:Tumor necrosis factor and interleukin
292:into "defense mode" by simulating an
169:. Egyptian physician Imhotep treated
663:
87:
1003:
630:
427:This kind of therapy is offered as
13:
361:
14:
1643:
1559:
1050:"Coley's Toxins Cancer Treatment"
1017:. 1 November 2008. Archived from
679:Kucerova P, Cervinkova M (2016).
1310:10.1111/j.1538-7836.2005.01110.x
1291:Zacharski L, Sukhatme V (2005).
649:. 22 August 2012. Archived from
335:
92:
1515:
1464:
1453:
1428:
1410:Borrell, Brendan (2008-02-18).
1284:
1249:
1229:
1202:10.1093/postgradmedj/79.938.672
1177:
1130:
1087:
1062:
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1033:
994:
944:
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876:
850:
845:Fever and cancer in perspective
455:According to an article in the
373:
340:Another hypothesis argues that
1237:"Proposed Mechanism of Action"
772:
721:
672:
657:
579:
282:
263:and sold under the trade name
1:
1632:Alternative cancer treatments
1436:"Waisbren Clinic – Home Page"
1354:10.1016/S0140-6736(01)05369-7
503:
163:
1577:
1571:Hospital for Special Surgery
1564:
1528:The Iowa Orthopaedic Journal
1270:10.1016/j.suronc.2006.05.002
966:The Iowa Orthopaedic Journal
859:"Fever, Pyrogens and cancer"
697:10.1097/CAD.0000000000000337
666:Postgraduate Medical Journal
274:
250:Food and Drug Administration
64:Hospital for Special Surgery
7:
906:10.1056/NEJM198708133170716
476:
324:(TNF). Tsung and Norton in
83:
10:
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1589:Coley Pharmaceutical Group
928:"A Commotion in the Blood"
797:10.7453/gahmj.2012.1.1.016
530:10.1517/13543784.16.9.1391
400:
356:thromboangiitis obliterans
287:One rationale argues that
153:
608:Hall, Stephen K. (1997).
246:Kefauver Harris Amendment
1138:"History and Background"
863:Landes Bioscience: Curie
616:. New York: Henry Holt.
1612:American Cancer Society
1172:Fever therapy revisited
1112:Hess, J David. (1997).
1015:American Cancer Society
747:10.4103/0976-9668.82318
457:Iowa Orthopedic Journal
223:American Cancer Society
200:John D. Rockefeller Jr.
40:mixed bacterial vaccine
1497:: 3377. Archived from
389:Drug makers including
347:Streptococcus pyogenes
209:Streptococcus pyogenes
45:Streptococcus pyogenes
1522:McCarthy, EF (2006).
1416:The Los Angeles Times
1385:International Surgery
1094:Germs As A Tumor Foe?
451:Professional politics
322:tumor necrosis factor
1584:MBVax Bioscience Inc
960:McCarthy EF (2006).
653:on 17 December 2019.
488:Cancer immunotherapy
466:alternative medicine
441:Hyperthermia therapy
437:active fever therapy
244:controversy and the
103:factual accuracy is
75:cancer immunotherapy
1482:Göhring, E (1985).
865:. Landes Bioscience
785:Glob Adv Health Med
332:, rather than TNF.
240:In the wake of the
215:Serratia marcescens
60:surgical oncologist
51:Serratia marcescens
1606:2015-04-26 at the
1595:Scientific reviews
1166:2009-12-11 at the
932:The New York Times
839:2009-12-11 at the
779:Kienle GS (2012).
734:J Nat Sci Biol Med
647:Cancer Research UK
318:lipopolysaccharide
148:Cancer Research UK
1258:Surgical Oncology
1099:Los Angeles Times
567:(6A): 3997–4002.
326:Surgical Oncology
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