Immune: A Journey Into the Mysterious System That Keeps You Alive

by Philipp Dettmer

An infamous example is TGN1412, a drug trial that went so horribly wrong that it reached beyond the sphere of immunology and got some headlines in newspapers. The trial was supposed to look for side effects in humans taking a drug that was supposed to stimulate T Cells in cancer patients and make them survive longer. The drug was an artificial antibody that was able to connect to and stimulate the CD28 molecule on T Cells—we already met CD28 before without naming it—one of the signals T Cells need to be activated. We described it as a gentle kiss the Dendritic Cell needs to give a T Cell to activate it. So the idea of TGN1412 is pretty straightforward: Give T Cells an artificial “kiss” to stimulate them to be more effective and easier to activate in cancer patients. Basically “boosting” their immune system to be more formidable in the face of this life-threatening disease. And yeah, well, boost it did. For safety reasons, the amount of TGN1412 administered was 500 times lower than the dose that had led to any reaction in macaques (which is a cute species of monkeys, if you are wondering) and so the researchers doing the drug trials did not expect any real reaction to occur in the human volunteers. But instead, minutes after TGN1412 was given to healthy young men, all hell broke loose. It turned out macaques, the animals used to test the drug in animal models, happen to have way fewer CD28 molecules on their T Cells than humans and so they reacted way less strongly to the d...