Downloaded from https://ashpublications. org/blood/article-pdf/124/3/310/1006801/310. pdf by Googlebot user on 11 October 2019 and CD123 1. 2 In a small phase 1-2 study, the authors report a high rate of complete remissions in patients diagnosed with BPDCN and receiving diphtheria toxin (DT)-IL3 as a single agent. This is a remarkable achievement. Apparently, malignant cells expressing IL3 receptors (CD123 is the a subunit of the IL3 receptor) bind and internalize the DT-IL3 fusion protein, leading to inhibition of protein synthesis and cell death (see panel B). In their paper, DT-IL3 is called SL-401

In a landmark paper,. 30 years ago, Thorpe et al suggested that DT could be engineered to kill leukemia cells. 3 Frankel et al fulfill that promise and produced a functional example of a DT fusion protein that demonstrates clear clinical benefit for patients with a hematological malignancy. The results of more advanced trials in the BPDCN population and treated with DT-IL3 are now eagerly awaited. Further, because these results were achieved with a single agent, future studies will undoubtedly strive to identify suitable agents to combine with DT-IL3 and improve its efficacy.