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To the Editor:
The recent tragedy, in which all active drug recipients developed life-threatening multiple organ failure during the phase I clinical trial of superagonistic anti-CD28 monoclonal antibody (TGN1412} (1), raised serious questions regarding the safety of human drug-trial participants. Results obtained in animal models do not always correspond to those observed in humans, and human cells placed in an in vitro culture environment may no longer exhibit physiologic functions that occur under natural conditions. An ideal precautionary method tor investigational drugs designed to be administered intravenously is to mix each drug candidate with whole blood in test tubes and evaluate both desired function and unexpected adverse reactions. Such an ex vivo test is completely safe and applicable to drugs acting on leukocytes. The biggest technical challenge, however, is to identify drug actions in whole blood in a short period of time, because longer incubations might be associated with secondary artifacts. Gene expression analysis is an interesting...