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Tregs control atherosclerosis

18.02.2013 - European researchers have shown that depletion of immunosuppressant T lymphocytes boosts hypercholersterolemia and atherosclerosis in mice.

The findings lay the foundation for cell-based therapies against the fatal disease. Until now, several studies had supported the assumption that FoxP3-positive CD4+CD25+ T cells block the inflammatory processes that lead to the formation of atherosclerotic plaques in the blood vessels, which can cause cardiac infarction and stroke. But the team under Göran Hansson from Swedish Karolinska Institute was the first to demonstrate the effect in genetically engineered DEREG mice. Those mice express the diphteria toxin (DT) under control of a Treg-specific FoxP3 promotor.

Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor–deficient (Ldlr/) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3+ Tregs. The depletion caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. The mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. The results prove that FOXP3+ Tregs block atherosclerosis by modulating lipoprotein metabolism.

The findings are good news for drug developers, as Milan-based researchers have recently demonstrated that it is feasible to isolate functional Tregs and expand them in vitro. The patent has already been licenced to German T-cell Europe, which will use the technology for inducing immune tolerance after organ transplantation.

© eurobiotechnews.eu/tg

http://www.european-biotechnology-news.com/news/news/2013-01/tregs-control-atherosclerosis.html

Industry reportGermany

27.04.2016 More revenue, more jobs, more financing, more R&D expenditure – all signs point towards sustainable growth in the German biotech sector. These are the results of the most recent company survey 2016, published by biotechnologie.de. The report was once again conducted alongside the biotech standards defined by the organisation for economic cooperation and development (OECD).

Clinical ResearchFrancePortugal

21.04.2016 An expert panel’s final report on the fatal drug trial earlier this year in France states that the death of one of the participants was most likely caused by the drug’s toxicity and not by any violation of the rules.

Immuno-oncologyNetherlandsBelgium

21.04.2016 For up to US$685m (€606m), Dutch ArgenX has outlicensed its human antibody programme ARGX-115 to AbbVie. The pre-clinical immuno-oncology candidate targets a protein believed to contribute to immunosuppressive effects of T-cells.

RegulatorySwitzerlandEU

20.04.2016 The US government is forking out up to US$100m to get Basilea Pharmaceutica’s broad-spectrum antibiotic ceftobiprole on the US market. In the EU, ceftobiprole is already available.

Immuno-oncologyUK

19.04.2016 British drug developer Heptares Therapeutics and mAb maker Kymab Ltd have partnered up in yet another immuno-oncology collaboration. The companies plan to discover antibody meds targeting a superfamily of receptors.

FinancingSwitzerlandFranceEUGermanyDenmark

15.04.2016 Not every company is put off by the current stock market climate. Swiss biopharma company GeNeuro has gone public at Euronext Paris, raising €33m in the process. Others, meanwhile, have to find different ways to raise money.

Event ReviewSwitzerlandBelgiumEU

13.04.2016 Despite political disturbances, 2015 was a good year for the biotech scene in Switzerland. Net sales increased by 5.1% to CHF5,133m and 400 additional people found jobs in the sector. As usual, the new numbers were presented at the annual Swiss Biotech Day – which set new records as well.

FinancingGermanyNetherlandsEU

12.04.2016 German-Dutch life science investment specialist Forbion Capital Partners has raised more than €180m for its venture capital fund Forbion Capital Fund III. Once more the money will primarily go to European start-ups.

Event ReviewGermanyEU

08.04.2016 Do you win by being innovative?, was the question asked at this year’s DIA Euromeeting in Hamburg. In a relaxed and cooperative atmosphere, regulators, physicians and patients had ample opportunity to interact with the healthcare industry.

M&AIrelandEU

07.04.2016 Pfizer and Allergan have called off their merger, cancelling plans to relocate the US pharma giant to Ireland to avoid US taxation. The US government has put a spoke in Pfizer’s wheels - an unfair move, Allergan says.

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