[3] 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.
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.
[22] Coley's toxins were also produced by the small German pharmaceutical company Südmedica[23] and sold under the trade name Vaccineurin.
Unlike hyperthermia, real fever not only means heating of the body but also higher activity of the immune system.
[27] The resulting fever from the lipopolysaccharide is thought to increase lymphocyte activity and boosts tumor necrosis factor (TNF).
[28] Another hypothesis argues that streptokinase (produced by killed bacteria of species Streptococcus pyogenes together with plasminogen from the patient) is the active agent of Coley's toxins.
For example, Dr Josef Issels used several unconventional and controversial treatments, including Coley's toxins, for cancer patients in the second half of the 20th century.
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) 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 alternative medicine is clearly flawed for the same reason that malariotherapy 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 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).