TGN1412: From Discovery to Disaster - PMC - PubMed Central …
Monoclonal anti-CD28 antibody such as TGN1412 was capable of activating T cells by binding to CD28 receptor irrespective of T-cell receptor activation and hence it was termed as a CD28 superagonist.
Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody ...
2006年9月7日 · Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that...
TGN1412: From Discovery to Disaster - PubMed
In 2006, a phase I clinical study was conducted for a CD28 superagonist antibody TGN1412 in six human volunteers. After very first infusion of a dose 500 times smaller than that found safe in animal studies, all six human volunteers faced life-threatening conditions involving multiorgan failure for which they were moved to intensive care unit.
Why was the cytokine storm not identified pre-clinically? Did pre- or post-clinical testing give insights? So what happened? The data show: How do we prevent this from happening in the future? We cannot, but...
Monoclonal antibody TGN1412 trial failure explained by …
TGN1412 is a superagonist CD28-specific monoclonal antibody (mAb) developed as an immunotherapeutic for the purpose of balancing the immune system (TeGenero, 2005). TGN1412 was called a ‘superagonist’ because it could activate T-cells without the need for prior engagement of the T-cell receptor complex (Tacke et al., 1997; Lühder et al ...
The storm has cleared: lessons from the CD28 superagonist TGN1412 trial
2012年4月10日 · When, on 13 March 2006, six healthy young men received an intravenous injection of TGN1412, a first-in-class superagonist monoclonal antibody specific for the T cell co-stimulatory molecule CD28,...
2006年5月25日 · However, TGN1412 is a new class of monoclonal antibody which has a stimulatory mode of action affecting certain types of cell in the immune system. In this case the resulting activity seen in humans was not predicted from apparently adequate pre-clinical testing.
The rise and fall of the CD28 superagonist TGN1412 and its return …
A phase I trial of the human CD28 superagonist TGN1412 failed in 2006 due to an unexpected cytokine release syndrome, but after it became clear that dose-reduction allows to preferentially address regulatory T cells also in humans, clinical development was resumed under the …
2016年8月24日 · TGN1412 emerged as the ideal drug candidate. However, TGN1412 is a genetically engineered humanised form of the anti-CD28 antibody from the investigational mouse. This is because the use of mouse antibody in humans would result in dysfunction of the antibody as well as immunogenic toxic responses.3
Monoclonal antibody TGN1412 trial failure explained by species ...
To date, no unequivocal explanation for the failure of TGN1412 to stimulate profound cytokine release in vitro or in vivo in species used for pre-clinical safety testing has been established. Here, we have identified a species difference almost certainly responsible for this disparate immunopharmacology.
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