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admin | Prevent Bv | 18.07.2014
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The potential of bacteria as anticancer agents lies within the ability of certain strict or facultatively anaerobic bacteria to selectively colonise tumour tissues. Spores of these anaerobic bacteria can only germinate and multiply in environments devoid of oxygen. Some bacteria are known to enhance the effectiveness of chemotherapeutic agents such as liposome-encapsulated drugs by facilitating their release within the tumours by liposomase. In the bacteria-mediated prodrug therapy (also known as suicide gene therapy), bacteria carry a gene coding for an enzyme that converts a prodrug-which is non-toxic- into a toxic drug. Alternatively, these bacteria can be genetically engineered to express cytotoxic enzymes such as cytokines that will directly destroy the tumour cells.
COBALT uses bacteria- directed anticancer treatments along with other conventional therapies such as chemotherapy or radiotherapy. Another prospective anticancer treatment combining radiotherapy and bacterial therapy has also been discovered recently.
Major advantage of using bacteria and bacterial derivatives as anticancer treatments is their selectivity towards the cancerous cells.
However promising, bacteria-mediated anticancer treatment is not without its own limitations. Despite these hindrances, the bacterial anticancer therapy shows great potential towards the future.
Recent interest in bacterial vectors as potentially useful in cancer therapy has arisen due to efforts to develop cancer vaccines. A live strain of the bacteria was engineered to allow recombinant antigenic proteins to be delivered to mice using the bacterial secretion system.
Concerns around using these type III vectors in clinical trials for immunotherapy centre around factors such as the intrinsic toxicity of the vectors.
Further work to help improve the performance of the vectors has focussed on injection frequency and interval in mice and on adoption of a dual antigen rather than a single antigen delivery vector. Altogether, the results of this group suggest potential for live attenuated type III secretion system-base P. DISCLAIMER: We take no responsibility for accuracy of information provided and do not endorse any research, advice or products. Large tumours mostly contain necrotic and hypoxic areas in the middle, providing ideal growth conditions for the growth of these bacteria. These spores, when injected systemically, will remain dormant in healthy oxygen rich cells and become active within the anaerobic and necrotic cancer tissues.
However, these bacteria do not completely destroy the tumour, thus necessitating the combination of bacterial therapy with other anticancer treatments such as radiotherapy, radioimmunotherapy, and chemotherapy.
Once within the target tissue, gene expression will occur in the bacteria thus producing the required protein that destroys the cancers.
These bacteria, favouring the anaerobic and necrotic conditions of the tumour microenvironment, start proliferation and growth within the tumours.

Tumour cells, essentially being parent’s own cells, fail to evoke sufficient immune responses in the host to be destroyed by the immune system. These toxins, after modifying their cellular affinities so that they will bind only to the cancer cells, can be used to control cancers.
This strategy thus far has been shown to significantly increase the effectiveness of oncolysis than the individual treatments.
Other therapeutic alternatives such as chemotherapy and radiotherapy are non-selective, thus damaging healthy tissues as well as cancer tissues.
One of the major drawbacks is the ability of these bacteria to cause diseases at the doses required for an effective tumouricidal effect. With the advent of genetic engineering and synthetic biological approaches, there is hope that it will be possible to come up with an efficient, safe and effective bacteria-mediated cancer treatment.
One type of bacterial vector that has attracted attention are the type III secretion system-based vectors.Studies from the Universite Joseph Fourier in Grenoble, France have focussed on a type III Pseudomonas aeruginosa vector with promising results. Using the vector to deliver ovalbuminin to the antigen-presenting dendritic cells of mice resulted in the mice mounting an ovalbumin-specific CD8(+) T lymphocyte immune response and to the mice being resistant to a subsequent challenge with an ovalbumin-expressing melanoma. The research group have addressed these issues by strategies such as deletion of quorum-sensing genes and the aroA gene.
These strategies have led to improvements in therapeutic efficacy, tumour rejection and safety. Fehleisen and the American physician William Coley were the first people to observe that bacterial infections reduced cancers in patients. These bacterial vectors, after being genetically altered, can transport anticancer drugs, cytotoxic peptides, therapeutic proteins or prodrug converting enzymes into the target site.
These proteins can be anticancer proteins, therapeutic proteins or prodrug converting enzymes. However bacteria, though stripped off their pathogenicity factors, can stimulate the immune system thus enhancing the antigenicity of the tumours. These toxins can be made safe to the healthy cells by either coupling them with a substance such as antibodies that bind specifically with the cancer cells or by genetically altering their cell-binding properties. Moreover, the bacteria are easy to produce in mass scale thus reducing the cost of production of drugs. Even after attenuation, some studies report the death of the animals after administrating these bacteria.
Also injection of the ovalbumin-delivering vector resulted in cure of five out of six mice that had been implanted with tumour.
Bacteria use quorum sensing of the local bacterial population density to coordinate behaviours such as biofilm formation. Safety has been further addressed by using a more attenuated mutant-CHA-OAL strain that is avirulent in mice. Optimization of a type III secretion system-based Pseudomonas aeruginosa live vector for antigen delivery. Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector.

Optimization of antitumor immunotherapy mediated by type III secretion system-based live attenuated bacterial vectors. In case some post damages your benefits or violate your rights, please report it and we'll remove it. For almost a hundred years, scientists have known the potential of using bacteria to alleviate certain cancers. They independently noticed that some of their patients suffering from cancers recovered after being infected by the bacterium Streptococcus pyogenes. Furthermore, bacterial toxins and bacterial spores also have a potential as antitumour agents.
Once within the tumour microenvironment, these spores can activate and proliferate thus colonising the tissues with the desired bacterial species. Bacteria selectively invade the cancer tissues and present bacterial antigens thus being targets for the host immune system. Another main problem is incomplete lysis of the tumours by the bacteria thus making it necessary for a secondary alternative treatment option. Quorum sensing allows communication within a species and between species.Its mutation was associated with a slight reduction in toxicity while mutation of aroA, which makes the strain auxotrophic for aromatic amino acids, led to strongly reduced toxicity. Now, with most of the other available anticancer therapies proving inefficient, the focus is back on the ability of these tiny bugs to cure cancers.
In the late 1800s, Doctor Coley developed a vaccine using the dead cells of two bacterial species, S. Furthermore, bacteria can act as immunotherapeutic agents, stimulating the immune system of the host against the cancer cells. The host immune system then destroys the bacteria infected tumour cells which would have otherwise evaded the attack.
Furthermore, these anaerobic bacteria can only target large solid tumours where there are anaerobic conditions favourable for their growth.
Combination of both mutations resulted in a highly efficient bacterial strain in terms of T cell activation.
Small non-necrotic secondary tumours are out of their reach, and as a result, there is a chance of the cancer being spread through these metastases. He also prepared 'Coley's toxins' - toxic derivatives of bacteria-as anticancer treatments which were the only systemic anticancer therapy available until the 1930s.
Subsequently, novel treatments such as radiotherapy, chemotherapy, and removal of cancer tissues by surgery were introduced and the interest was lost on the bacterial therapy.

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