Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers propose reason for severe side-effects of Northwick Park clinical trial

26.01.2007
A possible reason why the Northwick Park clinical trial of the drug TGN1412 caused multiple organ failure in human volunteers is revealed in research presented today at a conference near Paris.

The research shows that stimulating the molecule CD28 on cells that mediate the immune response, known as T cells, can have an adverse effect if these immune cells have been activated and altered by infection or illness in the past.

The scientists found that when they artificially stimulated CD28 on these previously activated 'memory' T cells, this caused the cells to migrate from the blood stream into organs where there was no infection, causing significant tissue damage. CD28 is an important molecule for activating T cell responses and the TGN1412 drug tested on the human volunteers strongly activates CD28.

Around 50% of adult human T cells are memory cells, having been activated by infections and illnesses during the course of a person's life. However, animal models, such as those used to test TGN1412 before tests were carried out on humans, do not have many memory T cells because they are deliberately kept in a sterile environment where they are shielded from infections.

The research, by scientists from Imperial College London, King's College London, and the Babraham Institute, is presented today at the Club de la Transplantation conference in Cernay la Ville, near Paris.

Dr Federica Marelli-Berg, lead author of the research from the Department of Immunology at Imperial College London, explained: "The drug TGN1412 appeared to be relatively safe when it was tested in animal models. However, when the drug was tested on human volunteers, some experienced very severe side-effects.

"Our research suggests that this is because the human subjects' memory T-cells lost their sense of direction and started migrating into several areas of the body where they were not supposed to go, and caused damage."

The researchers reached their conclusions after memory T cells in which CD28 had been previously stimulated were injected into healthy mice. These cells immediately migrated from the blood into many organs including the kidney, the heart and the gut, where they are not normally found unless there is an infection.

TGN1412 was developed to treat chronic inflammatory conditions, including rheumatoid arthritis, leukaemia and multiple sclerosis, which are caused by the body's immune system attacking itself. It was thought that by targeting CD28, the drug could over-stimulate the rogue T cells, making them burn out and die.

The study was funded by the British Heart Foundation.

Laura Gallagher | alfa
Further information:
http://www.imperial.ac.uk

More articles from Health and Medicine:

nachricht Observing the cell's protein factories during self-assembly
15.06.2018 | Charité - Universitätsmedizin Berlin

nachricht Scientists unravel molecular mechanisms of Parkinson's disease
13.06.2018 | The Francis Crick Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

Im Focus: Water is not the same as water

Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.

From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

A sprinkle of platinum nanoparticles onto graphene makes brain probes more sensitive

15.06.2018 | Materials Sciences

100 % Organic Farming in Bhutan – a Realistic Target?

15.06.2018 | Ecology, The Environment and Conservation

Perovskite-silicon solar cell research collaboration hits 25.2% efficiency

15.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>