Coley Toxins — The First Century

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8+ T cells

“…This is in contrast to studies with other bacterial species where only with live organisms such as mycobacteria does antigen gain access to the processing pathways for MHC class I presentation. 41,42 The suggestion that bacteria could be used for the treatment of malignancies stems back over 100 years with the use of Coley's toxins, 43 and the success of BCG as a treatment for bladder cancer has provided further evidence for the potential of bacteria-derived cancer vaccines. 44 Advances in our understanding of tumour immunology have allowed the combination of the nonspecific adjuvant effects that bacteria provide, along with the specificity of antigen-specific tumour CTL responses, linking innate and adaptive immunity.…”

Fever therapy revisited

“…It is apparent from her publications, but had escaped Coleys attention, that there was a correlation between the potency of a particular extract preparation to induce high fever and rate of curation: 3/13 different preparations had the highest rate of curation (survival longer than 10 years) and were the most powerful in inducing febrile reactions. Also, better clinical response correlated with duration of treatment: if the injections were given over 6 months, an astonishing 80% of inoperable sarcoma of soft tissues survived for 5 -88 years (Nauts and McLaren, 1990).…”

“…Unfortunately, Coley failed to establish a standard procedure but rather varied the regimen (extract preparation, treatment duration, injection frequency, injection site, dosage) throughout his career, making it difficult to compare his case studies and to pinpoint crucial parameters. His daughter Helen Coley-Nauts re-examined his case studies with respect to differences in bacterial preparation and clinical outcome (Nauts and McLaren, 1990). It is apparent from her publications, but had escaped Coleys attention, that there was a correlation between the potency of a particular extract preparation to induce high fever and rate of curation: 3/13 different preparations had the highest rate of curation (survival longer than 10 years) and were the most powerful in inducing febrile reactions.…”

“…Attempts to repeat his successes half a century later using these products were of mixed benefit. In few of these studies particular attention was paid to the induction of high fever possibly reaching 401C on one side and long treatment over at least several weeks on the other side, both of which appear to correlate with improved outcome (for reviews, see Nauts and McLaren, 1990;Hobohm, 2001). More important, in contrast to Coley's time, most of the patients treated with commercial extracts had prior or concurrent chemotherapeutic treatment with obvious immunocompromising effects, potentially diluting the effect of an immunostimulatory therapy.…”

Reassessing the Usual Suspects Causing a Commotion in the Blood (and Vessels?)

“…Although there were no prospectively controlled trials of Coley's toxins, there did remain a substantial anecdotal literature of case reports suggesting that some patients did benefit from the injection of the toxins. [1][2][3][4][5] Skeptics of the approach pointed to the lack of a known scientific mechanism underlying the approach; however, this all changed in 1975 when Lloyd Old and colleagues identified a serum factor that reproduced the ability of bacterial endotoxin to induce hemorrhagic necrosis of transplanted tumors in mice. 6 The protein, named tumor necrosis factor (TNF), turned out to be a pro-inflammatory cytokine with a multitude of diverse biologic activities.…”