But Dr Stephen Poole, speaking at the British Pharmacological Society’s Winter Meeting in Brighton today (Tuesday), said that research is still “ongoing” to understand why the drug had such an adverse effect in the clinic but not in pre-clinical testing.
Describing the incident as “the most obvious setback for medicines testing since thalidomide”, Dr Poole and his colleagues, from the National Institute for Biological Standards and Control (NIBSC) have, with new tests, successfully reproduced the devastating reaction suffered by the volunteers using human cells in the test tube (in vitro).
Standard preclinical in vitro tests on TGN1412 – the immunotherapy drug responsible for the Northwick Park disaster – failed to predict the catastrophic reaction that would occur when TGN1412 was administered to human subjects.
TGN1412 is from a class of drugs developed to re-balance the immune system for the treatment of autoimmune diseases, where the immune system has started to attack the body, such as rheumatoid arthritis and multiple sclerosis.
The Northwick Park disaster resulted in the UK Medicine and Healthcare products Regulatory Agency (MHRA) suspending all clinical trials of immunotherapy drugs and commissioning NIBSC, a government-funded institute, to investigate why both in vitro human cell tests and in vivo animal tests failed to predict the human immune system’s response to the drug.
“With hindsight testing this drug in man was a mistake, but at the time the standard required pre-clinical tests failed to predict the effects it would have on the six volunteers,” said Dr Poole, who said that the NIBSC’s group’s second paper on TGN1412 was due to be published shortly.
“While we are still investigating why the effect of this drug was so catastrophically different in the clinic than in pre-clinical testing, we have at least managed to develop new pre-clinical tests that should help us to avoid such outcomes in the future.”
Speaking at the British Pharmacological Society (BPS) conference, Dr Poole identifies new pre-clinical in vitro testing of immunotherapy drugs that should help prevent any repetition of the disastrous events that were witnessed at Northwick Park.
These measures include ensuring that such drugs are not tested solely on immune (white blood) cells in isolation. The NIBSC group has shown that having a mixed human cell culture of white blood cells and endothelial cells – the cells that line blood vessels – is a much better indicator of how this type of drug will react in vivo.
The NIBSC group has also developed a technique that dries the drug onto a plastic surface, rather than testing it on cells as a solution in water, which has proven to be a far more reliable indicator of how the drug will react in the human body.
“The aim of our research is to improve the preclinical testing of immunotherapy drugs on human cells in vitro, as well as to establish why the antibody was not toxic in pre-clinical testing,” said Dr Poole.
“We have made significant progress in designing new in vitro tests that hopefully will avoid the consequences that occurred at Northwick Park; indeed such tests could prevent harmful drugs of this type even reaching the animal-testing stage.”
Immunotherapy drugs have the potential to be incredibly important in the treatment of diseases that have so far eluded medical advances, including many forms of cancer, so it is vital that the scientific community has its faith in clinical trials and in immunotherapy fully restored.
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16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
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13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
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Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
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16.01.2017 | Power and Electrical Engineering