Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Salmonella as a tumour medication

23.10.2017

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target tumours and to colonise them. Researchers are aiming to make use of this property for cancer therapy, but they are facing a dilemma:


Electron microscopic image of Salmonella enterica (serovar Typhimurium).

HZI/Manfred Rohde

Salmonella infections are life-threatening. Scientists from the Helmholtz Centre for Infection Research (HZI) in Braunschweig now undertook a successful step towards the clinical application. They developed a Salmonella strain that induces only a harmless infection, but activates the immune system strongly enough to fight the tumours. Their results were published in the journal OncoImmunology.

Cancer diseases are some of the most common causes of death throughout the world, and they are still gaining in significance as the average general population gets older. However, we still do not have a satisfactory therapy for many types of tumours. One extremely promising approach is to involve the immune system in the control of the tumour.

Scientists from the HZI use Salmonella enterica bacteria to activate the immune system to tumours and to trigger an inherent defence reaction. In cancer patients, salmonellae colonise tumour tissue specifically, but the infection can take a life-threatening course. "For this type of tumour therapy, a strain of Salmonella must not only trigger a strong defence reaction of the immune system, but it must also not be too aggressive such that we can keep it in check," says Dr Sebastian Felgner, who is a scientist at the HZI.

The HZI researchers introduced genetic changes into the bacteria step-by-step and tried to find an optimal balance between safety and sufficient immune activation. "We changed numerous properties of the salmonellae, for example a component that eliminates the apparatus of motility and therefore restricts the mobility of the bacteria," says Felgner.

In order to increase the visibility of the bacteria to the immune system, the scientists also addressed certain other molecules in the membrane – which is the outer shell – of the salmonellae. This is where so called lipopolysaccharides consisting of sugar chains and lipid chains are anchored. These molecules reside on the surface of the bacteria and are recognised by the immune system as being foreign.

To hide themselves upon infection, salmonellae have a number of enzymes that cleave lipid chains as soon as they enter the host. "We switched off those cleaving enzymes in our Salmonella strain. As a result, the lipid chains on the surface of the bacteria are preserved in the patients and are quite visible to the immune system," says Felgner.

Following this scheme, the scientists introduced a number of other genetic modifications into their Salmonella strain and investigated the therapeutic effect in mice. In the course of this work, they successfully found a proper balance between attenuation of the bacteria and the intensity of the immune reaction, and even took another hurdle:

"One problem is that humans that have been exposed previously to the bacteria developed immunity against them and may possibly no longer respond to the therapeutic salmonellae," says Dr Siegfried Weiß, the former head of the "Molecular Immunology" department of the HZI, who now works at the Hannover Medical School. "Therefore, a therapeutic strain must be able to overcome this inherent protection of the body, since salmonella infections are rather common, especially in countries with poor hygienic conditions where large parts of the population are immune."

The numerous modifications introduced by the HZI researchers have now resulted in a Salmonella strain that mobilises the inherent defence even in mice that are immune to salmonellae. "Even tumours that used to be resistant to the strain are now eliminated by the immune system," says Weiß.

The research is being done in close cooperation with the "Infection Biology of Salmonella" young investigator group of Prof Marc Erhardt, who recently joined the Humboldt University in Berlin. A patent for the newly developed Salmonella strain has been filed. "Our strain is safe and at the same time effective enough for tumour therapy," says Sebastian Felgner. "The next step towards therapeutic application would be to test the strain in clinical studies in cooperation with industrial partners and to check its suitability for clinical application."

Original publication:
Sebastian Felgner, Dino Kocijancic, Michael Frahm, Ulrike Heise, Manfred Rohde, Kurt Zimmermann, Christine Falk, Marc Erhardt, and Siegfried Weiss: Engineered Salmonella enterica serovar Typhimurium overcomes limitations of anti-bacterial immunity in bacteria-mediated tumor therapy. OncoImmunology, 2017, DOI: 10.1080/2162402X.2017.1382791

The press release and a picture are also available on our website: https://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/salmonell...

Helmholtz Centre for Infection Research:
Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, are engaged in the study of different mechanisms of infection and of the body’s response to infection. Helping to improve the scientific community’s understanding of a given bacterium’s or virus’ pathogenicity is key to developing effective new treatments and vaccines. http://www.helmholtz-hzi.de/en

Contact:
Susanne Thiele, Press Officer
susanne.thiele@helmholtz-hzi.de
Dr Andreas Fischer, Editor
andreas.fischer@helmholtz-hzi.de

Helmholtz Centre for Infection Research
Press and Communications
Inhoffenstr. 7
D-38124 Braunschweig
Germany

Phone: +49 531 6181-1404

Susanne Thiele | Helmholtz-Zentrum für Infektionsforschung

More articles from Life Sciences:

nachricht Insect Antibiotic Provides New Way to Eliminate Bacteria
15.11.2018 | Universität Zürich

nachricht New findings help to better calculate the oceans’ contribution to climate regulation
15.11.2018 | Jacobs University Bremen gGmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Putting food-safety detection in the hands of consumers

15.11.2018 | Information Technology

Insect Antibiotic Provides New Way to Eliminate Bacteria

15.11.2018 | Life Sciences

New findings help to better calculate the oceans’ contribution to climate regulation

15.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>