Can bacteria shrink tumors?

Cancer Therapy: The Microbial Approach

n this age of advanced injected live Streptococcus medical science and into cancer patients but after I technology, we still the recipients unfortunately continue to hunt for died from subsequent innovative cancer therapies infections, Coley decided to that prove effective and safe. use heat killed bacteria. He Treatments that successfully made a mixture of two heat- eradicate tumors while at the killed bacterial species, By Alan Barajas same time cause as little Streptococcus pyogenes and damage as possible to normal Serratia marcescens. This Alani Barajas is a Research and tissue are the ultimate goal, concoction was termed Development Technician at Hardy but are also not easy to find. “Coley’s toxins.” Bacteria Diagnostics. She earned her bachelor's degree in Microbiology at were either injected into Cal Poly, San Luis Obispo. The use of microorganisms in tumors or into the cancer therapy is not a new bloodstream. During her studies at Cal Poly, much idea but it is currently a of her time was spent as part of the undergraduate research team for the buzzing topic in cancer Cal Poly Dairy Products Technology therapy research. Center studying spore-forming bacteria in dairy products. In the late 1800s, German

Currently she is working on new physicians W. Busch and F. chromogenic media formulations for Fehleisen both individually Hardy Diagnostics, both in the observed that certain cancers prepared and powdered forms. began to regress when patients acquired accidental erysipelas (cellulitis) caused by Streptococcus pyogenes. William Coley was the first to use

New York surgeon William bacterial injections to treat cancer www.HardyDiagnostics.com patients. Coley was the first to use

bacteria as a form of cancer therapy in the 1890s. He He treated more than 1,000 did not result in significant antibiotics. Abscess formation patients using this bacterial tumor regression. could be a potential side effect approach to cancer therapy. In the early 2000s, genetic of this treatment but can be However, Coley’s studies engineering allowed scientists managed and the risk were controversial and at Johns Hopkins University compared with the benefits difficult to repeat. His to create a strain of may be well worth it for approaches were further Clostridium novyi with a certain cancer types. disregarded with the deleted gene that codes for the emergence of radiation and lethal toxin produced by the Furthermore, it has been chemotherapy treatments in bacterium. They named this shown that C. novyi-NT the 20th century. organism C. novyi-NT (NT spores could result in a for non-toxic). Clostridium localized inflammatory Solid tumors contain areas of novyi is an obligate anaerobe response as well as an low oxygen, known as and is a ubiquitous organism, adaptive immune response hypoxia. These regions found in soil and feces. It is a against tumor cells (3). emerge when tumor cells pathogenic organism and is grow very rapidly, causing closely related to Clostridium The researchers that them to outpace the blood botulinum types C and D. conducted these studies supply that delivers oxygen to realized that successful results the tumor. Cancer cells in in lab rodents rarely translate hypoxic regions are highly to successful trials in people resistant to standard so they utilized canine models chemotherapy and radiation to demonstrate the plausibility therapies. Scientists of the treatment. discovered that certain anaerobic bacteria, such as Clostridium spp., were able to grow and live in oxygen-poor cancerous tissue but the Clostridium botulinum at 1,000X bacteria could not survive when coming in contact with Without the ability to produce oxygenated sides of the toxic proteins, C. novyi-NT tumor, thus causing no harm was a good candidate for Dogs were chosen because the to normal tissue. cancer treatment with the toxicities and effects from hopes of reducing tumor size therapeutic agents are similar In the 1950s and 1960s, while at the same time in dogs and people. Also, researchers used the anaerobic limiting side effects. canine soft tissue sarcomas bacterium Clostridium have clinical and butyricum to treat cancer C. novyi-NT spores injected histopathological features that patients. While the treatment into the brain tumors of rats resemble human soft tissue was successful in diminishing resulted in localized tumor sarcomas. C. novyi-NT spores tumor size, patients became necrosis and increased rat injected intra-tumorally sick from the toxins produced survival rate (2). Brain edema produced robust antitumor by the bacteria. Use of non- was common as a result of C. responses and adverse effects pathogenic Clostridium novyi-NT germination but were mild in severity, strains proved ineffective and abscess formation was not seen with the use of consistent with local infection does not cause illness in the addition to vaccinating against at the injection site (2). host and is incapable of tuberculosis, has been used as replicating in normal tissue an effective form of Safety trials were started in but can still grow in tumors immunotherapy for superficial humans and results have been where purine is available (4). bladder cancer. It is also positive though not perfect. commonly used to prevent The main issue with this type The less limiting recurrence of noninvasive of treatment has to do with the environmental conditions bladder cancer. fact that C. novyi-NT elicits a required for Salmonella local response and does not growth makes this organism The use of viruses in cancer target metastatic tumors, useful for treatment against therapy has also made article metastasis being the most small tumors, unlike headlines. Significant events lethal aspect of cancer. The Clostridium spp. which include a modified measles next step for these researchers cannot survive in aerobic virus that was able to almost is to determine which types of environments. completely eradicate tumors respond best to this myeloma in a 49 year old type of therapy and how Less direct ways of using woman, and a modified HIV- immune cells are stimulated bacteria in cancer treatment type virus used to treat to attack the tumor as well. are also being studied, such as leukemia in a young girl. Understanding the engineering bacteria to be mechanisms at work here can vectors for gene-directed lead to research on more enzyme prodrug therapy use effective cancer treatment. (4).

Bacteria belonging to other Most bacterial cancer genera have also been studied therapies are either early in in cancer therapy. A strain of development or are still Salmonella typhimurium with undergoing investigational two important genes deleted research, with the exception HIV can be modified for has also been developed for of Bacillus Calmette-Guérin therapeutic purposes. use in cancer treatment. (BCG). BCG is the only established cancer treatment Many of these oncolytic that utilizes bacteria. This is viruses (viruses that commonly recognized as the preferentially attack and kill vaccine used to provide tumor cells) have been protection from tuberculosis. genetically engineered from modified viruses. Viruses utilized in these studies have included herpes viruses, pox viruses and adenovirus. The

Salmonella typhimurium future of oncolytic viruses to be used in cancer therapy is The genes the organism lacks certainly a promising one and are required for causing toxic The BCG Vaccine we can look forward to shock in its animal hosts and upcoming research and for purine synthesis. Without It is an attenuated strain of clinical trials in this field. these genes, S. typhimurium Mycobacterium bovis that, in Cancer patients today have a variety of mainstream treatment choices that include surgery, radiation therapy, immunotherapy, and chemotherapy. These treatments have saved many lives and continue to be the best treatment choice for certain cancers but they are also not always one hundred percent effective and some are certainly not without their damaging side effects.

The use of microorganisms in cancer therapy research has come a long way since “Coley’s toxins” and the future looks bright, not only for advances in this field, but also for cancer patients that can receive this form of treatment.

References

1. Oelschlaeger, Tobias A. "Bacteria as tumor therapeutics?." Bioeng Bugs 1.2 (2010): 146-7. 2. Roberts, Nicholas J., et al. "Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses." Science translational medicine 6.249 (2014): 249ra111- 249ra111. 3. Agrawal, Nishant, et al. "Bacteriolytic therapy can generate a potent immune response against experimental tumors." Proceedings of the National Academy of Sciences of the United States of America 101.42 (2004): 15172-15177. 4. Patyar, S., et al. "Review Bacteria in cancer therapy: a novel experimental strategy." J. Biomed. Sci 17.1 (2010): 21-30.