Co-stimulators of drug-trial disaster identified
Enlarge image


Co-stimulators of drug-trial disaster identified

14.05.2012 - German researchers found a potential co-factor that triggered the cytokine storm, which led to hospitalisation of six volunteers treated with TGN1412.

Langen – A team of German researchers from the Paul-Ehrlich-Institut (PEI) has identified an important mechanism that can explain how immunotherapy drug TGN1412 might have triggered the catastrophic immune reaction responsible for the 2006 Northwick Park trial. The drug-trial disaster left six healthy volunteers hospitalised. The team, led by Zoe Waibler, reports that TGN1412-mediated T cell proliferation and cytokine release triggered by the superagonistic CD28-specific antibody, requires an interaction of an inducible co-stimulator on T cells (ICOS) with its ligand on endothelial cells (LICOS).  The team reports in the journal Blood. "We found that co-stimulatory ICOS-LICOS interaction between T cells and endothelial cells is critically involved in TGN1412-mediated effects."

The Phase I clinical trial of TGN1412 took place at an independent clinical trials unit at Northwick Park and St Mark's Hospital, London, on 13 March 2006. TGN1412 was intended for the treatment of leukaemia, multiple sclerosis and rheumatoid arthritis. Eight volunteers were given the drug or a placebo by intravenous infusion, with an interval of about 10 minutes between patients. Within minutes of the last patient being administered the drug, the first began to complain of headache, followed by fever and pain. The five other patients to receive TGN1412, as opposed to the placebo, became seriously ill soon afterwards. All six male volunteers experienced cytokine release syndrome (cytokine storms) with effects similar to those of people suffering a severe allergic reaction. Each of the men was hospitalised for several weeks, with the worst affected requiring hospital treatment for four months.  The drug developing company, TeGenero Immuno Therapeutics from Germany, entered into insolvency proceedings later in 2006. It assets were sold to German-Russian Theramab LLC, which develops TGN1412 under the new name TAB08 as therapy for B-cell chronic lymphocytic leukaemia and rheumatoid arthritis.


09.10.2015 The US pricing controversy is reverberating halfway across the globe. Shield Therapeutics has taken its IPO plans off the table. Market conditions are too volatile, the company says.


07.10.2015 T-cell specialist Adaptimmune Therapeutics plc needs more space for its R&D in immuno-oncology. The expanding UK company is building a major facility that will house 200 staff.

Drug DiscoveryGermany

06.10.2015 Evotec has been hired by the US National Cancer Institute (NCI) to provide compound management services to the Chemical Biology Consortium. The goal: the discovery of new cancer treatments.

Drug DevelopmentUKBelgium

01.10.2015 Autoimmune disease specialist Apitope has raised €12m in a Series B financing round and is relocating its UK headquarters to Wales.

Drug DevelopmentFranceEUFinlandSpainItalyAustria

01.10.2015 Paris-based BEAM Alliance, a network of companies working on novel antibiotics founded earlier this year, has released its first position paper.


29.09.2015 Swiss CNS specialist Asceneuron SA has raised CHF30m (€27.5m) in a Series A financing, winning Paris-based Sofinnova Partners as its largest investor.


28.09.2015 US company Aduro Biotech has acquired Dutch monoclonal antibody discovery and development firm BioNovion for €29m plus milestones.


24.09.2015 Nutrition company Nestlé is teaming up with biopharmaceutical company AC Immune SA to develop a Tau diagnostic assay for early Alzheimer’s.


22.09.2015 Bayer has taken another step in its restructuring and development as a life sciences company after splitting from all its chemical divisions.


18.09.2015 AstraZeneca has partnered up with the US Department of Health in order to accelerate the development of new antibiotics. The goal: to be prepared for multi-resistant bugs – and for bioterrorism.


All Events

Current issue

All issues

Product of the week


Stock list

All quotes


  • ZELTIA (E)4.12 EUR22.99%
  • WILEX (D)2.20 EUR10.00%
  • DEINOVE (F)6.85 EUR7.54%


  • IMMUPHARMA (UK)28.50 GBP-12.98%
  • BAVARIAN NORDIC (D)35.60 EUR-8.48%


  • THROMBOGENICS (B)4.08 EUR43.7%
  • OREXO (S)65.25 SEK40.9%
  • ZEALAND PHARMA (DK)155.00 DKK26.0%


  • THERAMETRICS (CH)0.04 CHF-33.3%
  • IMMUPHARMA (UK)28.50 GBP-30.1%


  • KARO BIO (S)43.10 SEK5221.0%
  • CHRONTECH PHARMA (S)0.34 SEK325.0%
  • GALAPAGOS (B)38.85 EUR237.5%


  • NEOVACS (F)0.72 EUR-76.7%
  • BIOTEST (D)19.00 EUR-74.8%
  • EVOCUTIS (UK)0.16 GBP-70.9%

No liability assumed, Date: 09.10.2015