The recent report by the MHRA on its investigation into the adverse effects in the TGN1412 trial1 concluded that an unpredicted biological action of the drug in humans is the most likely cause of the cytokine release syndrome seen in the trial participants.2 So do we have any idea on how could TGN1412 have induced a cytokine storm?
TGN1412 is a monoclonal antibody that targets the CD28 co-signaling molecule that is present on most human T-cells (>90% CD4+, ~50% CD8+).3 The antibody acts as a superagonist by binding the CD28 molecule at a site distinct from that bound by its normal ligand B7 and this effects a strong mitogenic activation of the T-cell.4 In the normal activation of T-cells, CD28 signalling is preceded by the initial triggering of the T-cell receptor for antigen (TCR) and this ensures the controlled activation of only T-cells specific for antigen in the immune response ...
