Scientists have developed a test that uses cells from a single donor’s blood to predict whether a new drug will cause a severe reaction in humans.
The test could avert disasters like the 2006 trial of the drug TGN1412, which led to six healthy young men being admitted to intensive care with multiple organ failure. The volunteers receiving TGN1412 experienced a catastrophic inflammatory reaction called a cytokine storm.
Cytokine storm reactions are a particular worry for new biological therapies, or “biologics”, which use biological material such as antibodies. Many blockbuster drugs such as the cancer drugs Herceptin and Avastin are biologics, as are around a third of medicines in the pharmaceutical pipeline. Because these medicines are specific to humans, they can cause severe reactions that don’t materialise in animal studies, so tests on human cells are essential.
However, cytokine storm side effects are hard to predict with tests were just one cell type is used, since they depend on interactions between blood cells and endothelial cells, which form the lining of blood vessels. But because endothelial cells are deep within the body, they are normally only grown from tissue removed in surgery or post mortem, or from umbilical vessels after birth.
Because of this, current tests use endothelial cells taken from vessels of one donor, and white blood cells from a different donor. When cells from two different donors are used, one may have an immune reaction to the other, meaning the system is already primed for inflammation before the drug is added. This can result in the test falsely showing a severe immune reaction to a drug that is safe.
Researchers at Imperial College London got around this problem by isolating stem cells from the blood of a volunteer, and using them to grow endothelial cells in a dish. They then took white blood cells which they added to the donor’s own endothelial cells to recreate the unique conditions found in their blood vessels. When TGN1412 was added to the test tube, the mixture of cells released a cytokine storm, as would happen inside the body.
The new method is better as it only requires blood from one donor and doesn’t mix cells from different people, with the advantage of making a more reliable test.
Professor Jane Mitchell, from the National Heart and Lung Institute at Imperial College London, who led the study, said: “As biological therapies become more mainstream, it’s more likely that drugs being tested on humans for the first time will have unexpected and potentially catastrophic effects. We’ve used adult stem cell technology to develop a laboratory test that could prevent another disaster like the TGN1412 trial.
“Drug companies have the technical capacity to start using this test now, but we’re working on developing an off-the-shelf kit which will make it easy to use on a large scale.”
Dr Daniel Reed, the first author on the study, said: ”A further benefit of this new technology is that personalised therapies can be tested to see how safe and effective they will be for an individual.”
The Latest on: Personalised therapies
via Google News
The Latest on: Personalised therapies
Alector: Targeted Therapies For Neurodegenerative Diseases
on May 20, 2019 at 9:43 am
Namely, it aims to "develop therapies that empower the immune system ... Opinions offered here are NOT personalized recommendations. Readers are expected to do their own due diligence or consult ... […]
Personalized Medicine Report 2019 - Scientific & Commercial Aspects 2018-2028
on May 20, 2019 at 6:45 am
Biomarkers play an important role in personalized medicine. Diagnosis is integrated with therapy for selection of treatment as well for monitoring the results. There is emphasis on early detection and ... […]
Microbiota Restoration Takes the Podium at DDW 2019: Investigational Microbiota-Based Therapies for Recurrent C. diff Highlighted
on May 17, 2019 at 8:44 am
For more information on Rebiotix and its pipeline of human microbiome-directed therapies for diverse disease states ... and development investment goes towards finding innovative and personalized ... […]
Roche's personalised medicine entrectinib shrank tumours harbouring NTRK, ROS1 or ALK gene fusions in children and adolescents
on May 17, 2019 at 5:34 am
"The STARTRK-NG study underscores the importance of combining comprehensive genomic profiling with targeted therapies and supports our approach to providing people with personalised medicines ... […]
'That may well be the future': Companies have poured $8.5 billion into creating a new version of a cutting-edge, highly personalized cancer treatment
on May 15, 2019 at 7:53 pm
Called CAR-T cell therapy, the current approach consists of collecting a patient's blood, reengineering their disease-fighting T-cells to better kill cancer tumors, and then putting the cells back in ... […]
Genentech’s Personalized Medicine Entrectinib Shrank Tumors Harboring NTRK, ROS1 or ALK Gene Fusions in Children and Adolescents
on May 15, 2019 at 2:00 pm
“The STARTRK-NG study underscores the importance of combining comprehensive genomic profiling with targeted therapies and supports our approach to providing people with personalized medicines ... […]
Prostate enlargement & chronic pelvic pain need Thermobalancing therapy
on May 15, 2019 at 2:51 am
A new scientific article: Personalized care using thermobalancing therapy can help men with chronic prostatitis / chronic pelvic pain syndrome to recover, will be published soon in the Personalized ... […]
Solid Bio’s Plunge Sends a Warning on Gene Therapies
on May 14, 2019 at 11:01 pm
It’s easy to get excited about gene therapies, a group of new medicines that have the potential to cure diseases in one treatment. The saga of Solid Biosciences Inc. is a reminder that tweaking genes ... […]
Quick Opens New Cell and Gene Therapy Center of Excellence Logistics Facility
on May 14, 2019 at 5:21 am
Supports Life Science Industry With Growing Trend of Personalized Medicine Research and Commercialization NEW YORK, May 14, 2019 /PRNewswire/ -- As the trend for cell and gene therapies are ... […]
Personalized 'Eye-in-a-Dish' Models Reveal Genetic Underpinnings of Macular Degeneration
on May 13, 2019 at 6:10 am
The most common treatment for AMD is injections of a drug that inhibits VEGF. This therapy blocks the formation of new blood vessels and leakage from abnormal vessels. "Since current AMD therapies ... […]
via Bing News