A hundred and thirty years of the same idea
Bacterial cancer therapy: from Coley’s toxins to a wild frog-gut isolate
Using bacteria against tumours is one of the oldest ideas in oncology and one of the least finished. Knowing the lineage is the only way to judge whether the 2025 Ewingella americana result is remarkable or merely the newest entry.
The idea began with a surgeon watching sarcomas shrink after erysipelas infections in the 1890s. It was pushed aside by radiotherapy and chemotherapy, revived by genetic engineering in the 1990s, and has produced two serious modern programmes — attenuated Salmonella Typhimurium VNP20009 and spore-forming Clostridium novyi-NT. Neither has become a standard therapy. What is unusual about the Ewingella americana result is that the organism is neither attenuated nor engineered.
1. Coley, and the observation everyone forgot
William B. Coley, a bone surgeon at what became Memorial Sloan Kettering, noticed in the late nineteenth century that sarcoma patients who developed erysipelas — a streptococcal skin infection — sometimes saw their tumours regress. From 1891 he began deliberately inducing infections, and later used killed bacterial preparations that became known as Coley’s toxins (McCarthy EF, Iowa Orthopaedic Journal 2006;26:154–158, PMID 16789469).
The results were inconsistent, the preparations were not standardised, and radiotherapy arrived. The idea went quiet for most of a century. What Coley had actually stumbled onto — that a violent innate immune response inside a tumour can break immune tolerance of that tumour — is precisely the mechanism the 2025 work reports in modern instrumentation.
2. The two modern programmes
Salmonella Typhimurium VNP20009
An attenuated strain with deletions in msbB and purI reducing septic shock potential and making it auxotrophic. It entered human trials, and remains the most-worked chassis in the field — the current literature is dominated by engineered versions carrying payloads: chemokines, interleukins, aptamer-drug conjugates. Representative recent work: Liu R et al., J Immunother Cancer 2025, PMID 40592739; Liu B et al., Biomaterials 2025, PMID 39531748.
Clostridium novyi-NT
An obligate anaerobe with its lethal toxin gene removed, delivered as spores that germinate only in the hypoxic tumour core — a targeting mechanism enforced by the organism’s own biology. Reviewed in Staedtke V et al., Genes & Diseases 2016, PMID 30258882, and Sharafabad BE et al., Curr Cancer Drug Targets 2023, PMID 37069721.
A useful general framing of the toolbox is Lin D et al., Biomaterials 2021, PMID 34534860, and a recent overview is Jayaprakash M et al., Biomedicine & Pharmacotherapy 2025, PMID 40967079.
3. Where Ewingella americana sits
| Coley’s toxins | Salmonella VNP20009 | C. novyi-NT | Ewingella americana | |
|---|---|---|---|---|
| Organism state | killed preparation | attenuated by deletion | toxin gene removed, spores | wild type, unmodified |
| Oxygen requirement | n/a | facultative anaerobe | obligate anaerobe | facultative anaerobe |
| Targeting | none — systemic immune effect | tumour accumulation | germination restricted to hypoxia | tumour accumulation, ~3000-fold in 21 h |
| Killing route | immune only | immune + engineered payload | lysis of hypoxic core + immune | secreted cytolysins + immune |
| Human data | historical case series | trialled in humans | trialled in humans | none |
The wild-type column is the interesting one, and it cuts both ways. An unmodified organism sidesteps the regulatory and manufacturing burden of a genetically modified therapeutic and the authors present that as an advantage — comparing favourably, in their words, with engineered bacterial therapeutics. It also means there is no engineered kill switch, no auxotrophy, no deleted toxin: the safety argument rests entirely on measured behaviour rather than on designed-in constraint.
4. The part nobody writes about: making a living medicine into a product
Every organism in the table above shares one unglamorous problem, and it is the problem Panacea Bio Chem builds instruments for.
A live biotherapeutic has to survive being manufactured, dried, stored, shipped and brought back to life at the point of use — at a known, reproducible count. Conventional freeze-drying is where that chain usually breaks: ice crystal damage during freezing, osmotic shock on rehydration, and the terminal warm-up that a standard cycle uses to strip the last bound water.
Panacea’s low-temperature lyophilisation ends sublimation at −8 to −10 °C and desorption at −3 to −5 °C, so the cake never meets the +40 to +60 °C overheat that costs binding affinity in a peptide and viability in a cell. Lyoprester™ is a proprietary Panacea Bio Chem dual-chamber cartridge platform developed and invented by Bogdan Dicoias; its parameters and composition are not publicly disclosed. In it the diluent is already present in its own chamber and reconstitution is an actuation — the bypass wets the cake from the base upward, with no vial, no separate diluent and no operator technique in the loop.
That is the chain from synthesis through the Peptourbillon range into the Lyoprester dual-chamber cartridge, and it is why the most demanding peptides in the world are preserved here. Panacea Bio Chem has published no work on Ewingella americana and this page asserts none — the organism’s science belongs to the groups cited throughout.
5. Trending in the field
6. References
- McCarthy EF. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthopaedic Journal 2006;26:154–158. PMID 16789469. PubMed record
- Staedtke V, Roberts NJ, Bai RY, Zhou S. Clostridium novyi-NT in cancer therapy. Genes & Diseases 2016. PMID 30258882. PubMed record
- Sharafabad BE, et al. Therapeutic potential of Clostridium novyi-NT in cancer. Current Cancer Drug Targets 2023. PMID 37069721. PubMed record
- Lin D, et al. Bacterial-based cancer therapy: an emerging toolbox for targeted drug/gene delivery. Biomaterials 2021. PMID 34534860. PubMed record
- Jayaprakash M, et al. Bacteria-mediated cancer therapy (BMCT): therapeutic applications, clinical insights, and the microbiome as an emerging hallmark. Biomedicine & Pharmacotherapy 2025. PMID 40967079. PubMed record
- Iwata S, et al. Discovery and characterization of antitumor gut microbiota from amphibians and reptiles. Gut Microbes 2025;17(1):2599562. PMID 41376334. PubMed record
